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NANOSCIENCE AND NANOTECHNOLOGY IN BIOLOGY AND MEDICINE (R01): PA-11-148

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Also note: Nanoscience and Nanotechnology in Biology and Medicine (R21) PA-11-149 Details at: http://grants.nih.gov/grants/guide/pa-files/PA-11-149.html

Components of Participating Organizations

National Institute of Biomedical Imaging and Bioengineering

National Cancer Institute

National Eye Institute

National Human Genome Research Institute

National Heart, Lung, and Blood Institute

National Institute on Aging

National Institute on Alcohol Abuse and Alcoholism

National Institute of Allergy and Infectious Diseases

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Drug Abuse

National Institute on Deafness and Other Communication Disorders

National Institute of Dental and Craniofacial Research

National Institute of Environmental Health Sciences

National Institute of General Medical Sciences

National Institute of Neurological Disorders and Stroke

National Institute of Nursing Research

Application Receipt/Submission Date(s): Multiple dates, see announcement

Nanoscience and nanotechnology refers to the understanding and control of matter at the atomic, molecular or macromolecular levels, at the length scale of approximately 1-100 nanometers. The objective of this FOA is to encourage the study of basic biological phenomena and engineer nanotechnology solutions that will enable biomedical breakthroughs in the diagnosis, treatment, and management of diseases and traumatic injuries. Research projects may include the development, modification, or integration of advanced nanotechnologies and nanoscience-based tools, methods, concepts, and devices in addition to engineering nanoscale structures and systems to study and understand biological processes in health and disease and to develop novel diagnostics and interventions for treating disease.

Nanotechnology emerges from the physical, chemical, biological, and engineering sciences, where novel tools and techniques are being developed to probe and manipulate single atoms and molecules. These tools have already enabled a myriad of new discoveries of how the properties of matter are governed by the atomic and molecular arrangements at nanometer dimensions. These discoveries have impacted manufacturing processes of a wide range of materials and devices resulting in substantial improvements of existing technology as well as entirely new technological innovations. For example, nanolithography is a very active area of research used to fabricate nanometer-scale structures, meaning patterns with at least one lateral dimension between the size of an individual atom and approximately 100 nm. Others areas include atomic layer deposition and scanning probe microscopy coupled with corresponding advances in supramolecular chemistry. The ability to control the design properties of materials and devices at the nanoscale is also possible by exploiting strategies that are frequently complemented by bottom up engineering approaches. With the state-of the-art engineering techniques in materials science today, nanoscience and nanotechnology-based approaches are well poised to revolutionize research in biology and medicine.

Studies that employ nanotechnology techniques and concepts and are focused on biological processes will also give completely new insights into the physical relationships between cellular components and functional irregularities that trigger pathological abnormities. Here, nanotechnology and nanoscience offer a means to control the design and assembly of biomolecular processes relevant in health and disease. For example, the processes involved in energy conversion have been studied for many years through enzymology and structural biology, advances in the development and adaptation of nanotechnology and nanoscience-based approaches have the potential to construct a biomolecular machine that uses biological energy sources such as ATP or electrochemical gradients in novel ways. The successful design and development of such biomolecular machines would demonstrate understanding of a key biological process and create opportunities for interventions based on engineering principles. Ultimately, it will be possible to understand cells from a genetic, biochemical, physiological, and engineering perspective, thus enabling the fabrication of nanoscale modules de novo for therapeutic applications. The nanoscale engineering principles derived could also lead to novel bioinspired systems and architectures, such as biocompatible nanomachines incorporating polymer-based motility inspired by lessons learned from the study of biological models.

Nanotechnology can also be used to design multi-functional and multi-analyte diagnostic systems that not only define early stage changes or progression to a disease state, but also allow the identification of unique biological molecules, chemicals and structures not addressable by current assays. Nascent nanotechnology-based imaging agents for inflammation, metastasis, and angiogenesis are also emerging while nanoscale multifunctional materials, capitalizing on progress in genomics and proteomics, allow targeted delivery of molecular therapies with enhanced efficacy. Significant progress in the engineering of nanoprobes for imaging of cellular events, nanosensors to identify multi-functional analytes create opportunities to observe phenomena at the molecular level and allow researchers to study the function of biomolecules, supramolecular assemblies and organelles of living cells for further manipulation. Despite such emerging technologies, much more progress is still needed to adapt and translate nanoscience and nanotechnology solutions to biomedical innovation and applications.

For the purpose of this FOA, the proposed nanotechnology and nanoscience-based projects must target a specific problem or need in biology or medicine. Applications proposing only the use of commercially available nanoscale tools (e.g. commercial quantum dots as imaging agents) to study biological processes without specific technology development or application elements specific to biological processes are not appropriate for this initiative. Nanomaterial researchers are also encouraged to adopt standards, enable data sharing, and promote interoperability.

Because this subject matter encompasses a broad spectrum of research opportunities, applicants are encouraged to review and consider the focus areas identified by the participating NIH institutes outlined below. It is also important to note that research ideas and concepts designed to meet the goal of this FOA are not limited to these institute-specific interests or the areas described above.

Participating NIH Institutes and Centers have identified areas of interests in nanoscience and nanotechnology research relative to the goals of this FOA. This list is not meant to be exhaustive, exclusive, or to limit creativity and innovation, but rather illustrations of studies relevant to this FOA.

The National Cancer Institute (NCI) is interested in the development of, but not limited to, the following research areas:

  1. Nanotechnology-based diagnostic assays and imaging devices that would provide significantly improved sensitivity, specificity and selectivity in cancer detection;

  2. Nanotechnology-based in vivo drug delivery techniques allowing for a significant increase in therapeutic index of the treatment;

  3. Cancer theranostics with improved targeting, biocompatibility and imaging contrast capability;

  4. Paradigm-shifting approaches to nanomaterials fabrication for cancer applications that could lead, e.g., to improved control of size, shape, surface characteristics, and lower fabrication costs.

NCI's specific areas of focus and application include:

  1. Nanotechnology-based techniques enabling understanding, prevention, detection, and elimination of metastases,

  2. Nanotechnology-based techniques enabling understanding and overcoming of multi-drug resistance phenomenon (MDR),

  3. Nanotechnology tools and devices aimed specifically at monitoring of the tumor mecroenvironment, its heterogeneity, and its changes during tumorogenesis,

  4. Nanotechnology-based techniques for improved immunotherapies,

  5. Nanotechnology tools and devices which can penetrate cellular barriers that may limit devices accessibility to intended targets (notably including the blood-brain-barrier),

  6. Nanotechnology-based techniques allowing for capture, monitoring, and characterization of circulating tumor cells (CTCs),

  7. Methodologies for predictive modeling and understanding of nanomaterials' pharmacokinetics and pharmacodynamics in in-vivo environment.

The National Eye Institute (NEI) is interested in research and development involving nanoscience and nanotechnology approaches for the visual system in health and disease including, but not limited to:

  1. Drug delivery systems,

  2. Tissue engineering (self-assembly),

  3. Biotic-abiotic interface with respect to implants and prosthetics.

The National Human Genome Research Institute (NHGRI) is interested in research involving, but not limited to, nanoscience and nanotechnology to develop:

  1. Innovative techniques for DNA sequencing;

  2. Novel hybridization/probe-based nucleic acids tools for high throughput assays that enable, for example, gene expression analysis, genotyping, and single nucleotide polymorphism detection and scoring, and epigenomics assays.

The National Heart, Lung, and Blood Institute (NHLBI) is interested in the use of nanotechnology for the diagnosis and treatment of heart, lung, and blood diseases. Examples of NHLBI interests include, but are not limited to:

  1. Development of targeted nanomaterials for the diagnosis and/or treatment of cardiovascular, lung, and blood diseases with a specific emphasis on: (i) Development of novel small molecule targeting agents for site specific delivery of the nanomaterials and (ii) Incorporation of therapeutic payload and/or imaging beacon;

  2. Development of novel nanomaterials as artificial blood substitutes;

  3. Development of nasal delivery nanomaterials targeted to image and/or treat pulmonary diseases

  4. Development of nano-structured surface coatings on mechanical devices to reduce thrombosis and/or infection;

  5. Development of nano-scaffolds to promote myocardial regeneration.

The National Institute on Aging (NIA) is interested in research and development such as, but not limited to:

  1. Nanomaterials or nanoprobes for imaging, detecting and measuring biological processes that change in cells, tissues and organs with age and age-related disease;

  2. Development of nanomaterials for diagnosis or biomarkers of age-related disease and associated loss of tissue function;

  3. Design of nanoparticles or devices for novel drug delivery and/or for functional tissue repair and regeneration.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is interested in projects to design, develop or make use of nanoscale devices for, but not limited to:

  1. Determination of in vivo alcohol and alcohol metabolite concentrations (biosensors);

  2. Monitoring acute and chronic effects of alcohol exposure (biomarkers);

  3. Tissue-specific imaging and monitoring of alcohol actions;

  4. Optimizing drug delivery including tissue (e.g., CNS, liver and lung) and subcellular (e.g., mitochondrial)-targeting.

The National Institute of Allergy and Infectious Diseases (NIAID) is interested in projects implementing nanoscience and nanotechnology to address, but not limited to, the following priorities:

  1. Nanotechnology-based delivery systems for: (i) Chemo-immuno-therapeutics and prevention approaches including vaccines and topical microbicides and (ii) Pathogen-specific targeting,

  2. Tools and approaches to understand viral, bacterial, and fungal pathogenesis and host cellular immune response to allergens and/or infecting pathogens;

  3. Bio-imaging applications for disease and treatment evaluation;

  4. Rapid and potentially cost effective platforms for pathogen detection, resistance evaluations, host response, biomarker evaluation, and genetic testing in early and established disease;

  5. Interrogation of the safety of current and proposed nanotechnology platforms and strategies.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is interested in research and development involving nanoscience and nanotechnology approaches for musculoskeletal and skin health and disease in the areas of, but not limited to, implants, imaging, drug and gene delivery, and functional tissue engineering.

The National Institute of Biomedical Imaging and Bioengineering (NIBIB) is interested in nanoscience and nanotechnology as it relates to the Institutes' scientific program areas (http://www.nibib.nih.gov/Research/ProgramAreas) with particular emphasis on, but not limited to, the:

  1. Development of enabling nanotechnologies for drug and gene delivery systems and devices, sensors and micro/nanosystems, and tissue engineering;

  2. Development of new sets of design principles to generate biomaterials with nano-level interfacial properties for tissue engineering, implants, and medical devices;

  3. Development of techniques to characterize the physical, chemical, structural, and biological properties of nanostructured assemblies/materials to advance biomedical technologies;

  4. Development of new materials processing methodologies for the synthesis, and/or optimization, of new or existing nanomaterials for biomedical applications;

  5. Research and development of nanomaterials and structures for novel biomedical imaging agents and molecular probes targeting preclinical and clinical applications;

  6. Research and development of nano-scale technologies for biomedical imaging;

  7. Development of predictive models and simulations for understanding nanomaterials in vivo performance (e.g, compatibility, therapeutic efficacy).

The National Institute of Child Health and Human Development (NICHD) is interested in projects that utilize nanoscience and nanotechnologysuch as, but not limited to:

  1. Build devices that integrate with dysfunctional tissue;

  2. Selective delivery of drugs and gene products;

  3. Nanotexturing of surfaces and effects on cells and microorganisms;

  4. Manipulation of cells with carbon nanotubes and interaction of cells and nanotubes;

  5. Supporting the development of point of care applications that will improve the quality and access to care for women and children;

  6. Supporting safe use of nanomaterials during pregnancy;

  7. Supporting the development of new, and the improvement of existing, micro/nanofluidic technologies to treat infertility, preserve fertility and derive therapeutic cells from stem cells.

The National Institute on Drug Abuse (NIDA) is interested in research projects on, but not limited to:

  1. Drug development and nano formulations of existing therapeutic drugs;

  2. Selective and controlled drug delivery;

  3. Molecular and cellular imaging

The National Institute on Deafness and Other Communication Disorders (NIDCD) is interested in projects that utilize nanotechnology to address normal and disordered processes of voice, speech, language, smell, taste, balance and hearing such as, but not limited to:

  1. Medical implant surface coating for enhanced integration with neural or other biological tissues;

  2. Targeted delivery of drugs, genes and other small molecules;

  3. Therapeutics to better detect or treat disordered processes, such as biofilm formation in the middle ear.

The National Institute of Dental and Craniofacial Research (NIDCR) is interested in research projects that focus on nanoscience and nanotechnology approaches such as, but not limited to:

  1. Understand, control and manipulate cellular process of orofacial structures (e.g., tooth, salivary glands, bone, muscles);

  2. Develop new materials with novel properties for the repair of tooth decay and periodontal disease;

  3. Develop new technologies for the study and the prevention of oral biofilm formation.

The National Institute of Environmental Health Sciences (NIEHS) is interested in research projects such as, but not limited to, the:

  1. Evaluation of individual exposure to toxicants both external and internalized dose;

  2. Evaluation of the biological response to toxicants and the correlation of response to exposure with the etiology and progression of disease and dysfunction;

  3. Development of nanotherapeutic applications of nanotechnology to interfere in the influences of environmental factors on disease processes.

The National Institute of General Medical Sciences (NIGMS) is interested in research projects such as, but not limited to, the:

  1. Development of materials/methods for imaging subcellular structures at the nanoscale in living cells;

  2. Detection and manipulation of single molecules in vitro & in vivo;

  3. Development of new tools to query subcellular processes at the nanoscale

The National Institute of Neurological Disorders and Stroke (NINDS) is interested in research leading to the development and demonstration of, but not limited to:

  1. Nanoscale materials that modulate differentiation, plasticity, and repair within the nervous system;

  2. Nanoscale interfaces for stimulation and recording from the nervous system in health and disease;

  3. Biodegradable multifunctional nanoparticles for imaging and monitoring of the nervous system;

  4. Nanoscale imaging technologies for neuropathologies;

  5. Nanoscale approaches for pharmacological and gene-based therapies to cross the blood brain barrier.

In addition, NINDS is interested in work to understand the interactions at the nanoscale that control growth cone dynamics, axonal guidance, dendrite formation, synaptogenesis, or neurodegenerative processes.

The National Institute of Nursing Research (NINR) is interested in applications such as, but not limited to:

  1. Interdisciplinary research in nanotechnology;

  2. Risk and benefits of nanotechnology;

  3. Development of sensing technologies that enable real-time monitoring of health indicators and responses to treatment for individuals self-managing their chronic conditions;

  4. Technology applications for early detection of disease in at-risk populations;

  5. Systems of targeted drug delivery to treat severe pain and to provide palliation at the end of life.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations:

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

  • All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-148.html.

BIOMARKERS OF INFECTION-ASSOCIATED CANCERS (R01): PA-11-158

Also note: Biomarkers of Infection-Associated Cancers (R21): PA-11-159 Details at: http://grants.nih.gov/grants/guide/pa-files/PA-11-159.html

Components of Participating Organizations

National Cancer Institute

National Institute of Dental and Craniofacial Research

Application Receipt/Submission Date(s): Multiple dates, see announcement

This funding opportunity announcement (FOA), issued by the National Cancer Institute (NCI) and the National Institute of Dental and Craniofacial Research (NIDCR), of the National Institutes of Health (NIH), encourages the submission of Research Project Grant (R01) applications from institutions and organizations that propose to identify biomarkers for cancers where the etiology of the disease is attributed to infectious agents.

Infection-associated cancers are increasing at an alarming rate. Approximately 15 percent of cancers (about 1.5 million cases per year, worldwide) are linked to viral (11 percent), bacterial (4 percent), and other pathogens (0.1 percent), and the prevalence of these infectious agents is rising. Although the number of people infected is very high, only a minor proportion ever develops cancer. Furthermore, etiologic links between newly identified infectious agents, such as the xenotropic murine leukemia virus-related virus (XMRV) and cancer, have recently been suggest but remain to be firmly established. The objective of this FOA is to foster research to increase our knowledge of infectious agent-associated malignancies and identify those who are at increased risk of developing cancer among infected individuals and to detect early stage cancers in this population. In many cases, the infectious agents are widely present in humans, but only a small fraction of infected individuals develop cancer. For example, 10 million women in the U.S. have cervical human papillomavirus infections, but only 15 thousand develop cancers. In addition, only 1 percent of Helicobacter pylori-infected persons will develop gastric cancer. Thus, it is important to identify subpopulations of exposed individuals who are likely to develop cancer and to develop sensitive and specific screening tools to monitor for early stage cancers in infected populations. Identifying these subpopulations has proven difficult. Molecular markers provide a potential tool to identify the at-risk subpopulation and the presence of early stage cancers. These molecular markers must therefore be able to distinguish ordinary infections per se from infections that contribute to the development of cancer.

Cancer-associated infectious agents likely act, at least in part, by predisposing the cell to oncogenic changes that contribute to the progressive steps leading to cancer. It is very likely that these processes lead to a microenvironment conducive to cellular transformation resulting in the development of cancer. Thus, it is important to identify molecular changes that occur during the progression to cancer in infected cells and the tumor microenvironment. It is likely that distinguishing cells destined to become cancerous from all infected cells will require the identification of differential expression patterns of multiple molecular markers, i.e., generating molecular signatures that are specific for risk of developing cancer. These molecular signatures must permit reliable and accurate identification of at-risk individuals at a stage early enough to allow for effective intervention. Molecular profiles may be used to identify lesions associated with a high risk of developing cancer to help distinguish high-risk populations. Molecular analyses will also provide valuable insights into the mechanisms by which infectious agents promote cancer and may help identify potential targets for early detection and cancer prevention.

Humans are colonized by complex microbial communities, or microbiomes, which are thought to play an important role in human physiology. It is now appreciated that microbial community structure or composition contributes to health or disease. Recently, changes in the composition or diversity of microbial communities (dysbiosis) have been reported to be associated with numerous diseases including cancer. In one recent study, the esophageal microbiome of patients with gastroesophageal reflux disease (GERD), including Barrett's esophagus (a precursor lesion for developing esophageal adenocarcinoma), was shown to be distinct from that of healthy controls. Thus, in addition to specific bacteria or viruses, abnormal microbial communities can also be considered pathogenic. The development of high-throughput sequencing technologies and bioinformatic infrastructure, supported in part by Human Microbiome Project (HMP), has revolutionized the sampling, identification, and analysis of the human microbiome. Outstanding questions in microbiome research are whether particular body sites (in particular, gastrointestinal, skin, urogenital, and oral cavity) are associated with a core healthy microbiome, whether core microbiomes are stable across body sites and across time, how microbiome structure changes in health and disease, whether changes in microbiome structure directly drive the disease process or are only indicators of an altered/distressed tissue, and the relationship between host genotype and microbiome composition. Microbiome-focused studies are leading new research efforts in basic and applied research to develop innovative strategies for the diagnosis, prevention, and treatment of human disease and cancer.

There are relatively few reports on precancer molecular markers of infected hosts. With the advent of high-throughput molecular profiling technologies (e.g., gene microarrays, antibody arrays, and peptide mapping using mass spectrometry), it has become easier to identify molecular signatures of infected host cells and to perform correlative studies in the attempt to identify high-risk populations in an efficient and timely fashion. Proposed studies should apply these technologies or others so that disease-specific markers and/or profiles can be recognized and used to identify infected individuals in whom infected cells are progressing into cancer to distinguish high-risk populations.

The long-term goal of this FOA is to encourage research that will increase our knowledge of infectious agent-associated malignancies and utilization of molecular profiles in early detection, risk assessment, and prevention of cancer. For example, infections with Hepatitis C and B viruses are major risk factors for hepatocellular cancer, but most infected individuals do not develop cancer. If detected early, the 5-year survival rate for hepatocellular carcinoma following liver transplant is greater than 80 percent. However, most hepatocellular cancers are detected at late stages when there are few effective treatment options. Human papilloma virus (HPV) is responsible for as many as 100,000 cases of head and neck squamous cell carcinomas worldwide per year, the majority of which are oropharyngeal and tonsillar cancers. In the United States (U.S.), prevalence estimates of oral HPV infection ranges from 9.2 to 18.6 percent. The incidence of tonsillar cancer in the U.S. has increased by 2 to 3 percent per year from 1973 to 1995. HIV-infected individuals have a 2- to 6-fold increase in risk of developing oropharyngeal and tonsillar cancers. Nasopharyngeal carcinoma (NPC) is a malignant neoplasm of the nasopharynx that is associated with Epstein-Barr Virus (EBV) infection. NPC is rare in most parts of the world, but it is an important health problem in China and Southeastern Asia. Molecular signatures that either distinguish individuals with infectious agents who are at high risk of developing cancer or detect early stages of cancer in infected individuals would result in early detection and reduced mortality. These molecular approaches provide snapshots of how infectious agents promote cellular transformation through altered biology of the infected cells and their interactions with the host environment. The NCI recognizes signatures of cancer cells, gene-environment interactions, and tumor microenvironments as high priority areas.

This initiative encourages research to identify molecular markers for risk assessment and early detection in individuals exposed to infectious agents that have been linked to cancer. Listed below, but not limited to, are several programmatic areas in need of support for developing molecular signatures for infectious agent-associated cancers.

  • I. Molecular profiles of normal, precancerous, and cancerous lesions following infection and of body fluids from infected individuals: Infectious agents interact with host cells and activate sets of infectious agent-specific and host-specific genes and proteins. Often some of these proteins are secreted into extracellular fluids. Samples utilized for studies may be derived from tissues or body fluids (e.g., serum, nipple aspirate, pancreatic juice, sputum, urine, alveolar lavage, saliva, stool). It is advantageous if marker profiles can be obtained from body fluids that are collected using minimally invasive methodologies. In addition, chronic inflammation in response to the infectious agent may play a role in cancer development. It may be possible that indicators of inflammation or immune activation could also be useful indices of cancer predisposition.

  • II. Evaluation of these molecular profiles for use in gaining a better understanding of the role of infectious agents in cancer development and use in early detection, risk assessment, and prevention of cancer: In all known cases, infectious agents that are associated with cancers persist for long periods in the host before cancer develops. How the host responds to the infectious agents and how the agent modulates this response are critical in allowing for its persistence and may determine the risk of cancer. Molecular profiles should be analyzed to determine whether a single biomarker, panel of biomarkers, or molecular patterns can be used to determine which infected individuals are at risk of developing cancer and to determine the transition from chronic infection to the initiation of cancer. These molecular profiles may also be used to identify targets for cancer prevention and therapeutic vaccine development.

Research projects proposed in the applications may involve a number of infectious agents showing associations with cancer. Noteworthy viral agents of interest to this program are human papillomavirus (HPV), Hepatitis B and C viruses, Epstein-Barr virus (EBV), xenotropic murine leukemia virus-related virus (XMRV), and Simian Virus 40 and Merkle cell polyomaviruses. Furthermore, an escalating prevalence of early cervical, lung, and colon cancers has emerged among HIV patients. Applicants are also invited to investigate bacterial etiology in cancer, such as the role of Helicobacter pylori in thedevelopment of gastric cancers. In addition, studies aimed at investigating associations between altered microbiome composition and cancer to establish microbiome signatures as biomarkers for cancer or as mechanistic bases for cancer development and progression are encouraged. The involvement of parasitic infections in various cancers is also relevant to this FOA. The National Institute of Dental and Craniofacial Research (NIDCR) has particular interest in EBV- and HPV-associated head and neck cancers, including oral and oropharyngeal cancers in both HIV-1-infected and non-HIV-1-infected populations. NIDCR also supports infectious-associated tumors (benign and malignant) of the salivary glands. Research projects covering basic science (infectious life cycle, viral replication, etc.) or treatment studies of these infectious agents without direct relevance to cancer biomarker development are not encouraged by this FOA.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); for profit organizations; small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-158.html.

THE EFFECT OF RACIAL AND ETHNIC DISCRIMINATION/BIAS ON HEALTH CARE DELIVERY (R01): PA-11-162

Also note: The Effect of Racial and Ethnic Discrimination/Bias on Health Care Delivery (R21): PA-11-163 Details at: http://grants.nih.gov/grants/guide/pa-files/PA-11-163.html

Also note: The Effect of Racial and Ethnic Discrimination/Bias on Health Care Delivery (R03): PA-11-164 Details at: http://grants.nih.gov/grants/guide/pa-files/PA-11-164.html

Components of Participating Organizations

National Cancer Institute

National Heart, Lung, and Blood Institute

Application Receipt/Submission Date(s): Multiple dates, see announcement

This funding opportunity announcement (FOA) encourages the submission of research project grant applications from institutions/organizations that propose to: (1) improve the measurement of racial/ethnic discrimination in health care delivery systems through improved instrumentation, data collection, and statistical/analytical techniques; (2) to enhance understanding of the influence of racial/ethnic discrimination in health care delivery and its association with disparities in disease incidence, treatment, and outcomes among disadvantaged racial/ethnic minority groups: and (3) to reduce the prevalence of racial/ethnic health disparities through the development of interventions to reduce the influence of racial/ethnic discrimination on health care delivery systems in the United States (U.S.).

Racial/ethnic minorities suffer disproportionate morbidity and mortality from chronic diseases such as cancer, heart disease, diabetes and stroke. Although racial/ethnic differences in morbidity and mortality can be partially explained by differences in lifestyle, health behavior and financial access to care, these factors do not entirely explain differences in incidence, treatment or outcomes. The Institute of Medicine (IOM) report on unequal treatment (http://www.nap.edu/openbook.php?isbn=030908265X) as well as several other reviews show that racial/ethnic minorities also less frequently receive appropriate care which has an adverse impact on their health outcomes including higher recurrence rates, poorer survival experiences and higher morbidity and mortality. An association between perceived discrimination and poorer health status has also been found. The IOM report concluded in part that "(1) Racial/ethnic disparities in healthcare occur in the context of broader historic and contemporary social and economic inequality and evidence of persistent racial and ethnic discrimination in many sectors of American life; (2) health systems, healthcare providers, patients and utilization managers may contribute to racial and ethnic disparities in healthcare; and (3) that health provider bias, stereotyping, prejudice and clinical uncertainty may contribute to racial and ethnic disparities in health care."• The Trans-US Department of Health and Human Services Health Disparities Progress Review Group also recognized the need to discuss the impact of racism as a fundamental cause of health disparities.

The IOM committee recommended that additional research be conducted to provide insight into how and why racial/ethnic disparities occur and to test interventions and strategies to eliminate them, including research that provides further elucidation on: (1) patient, provider and institutional contributions to healthcare disparities; (2) the relative contributions of provider bias, stereotyping, prejudice, and uncertainty to racial/ethnic disparities in diagnosis, treatment, and outcomes of care; and (3) the role of non-physician healthcare professionals, pharmacists, allied health professional and non-professional staff contribution to healthcare disparities.

The National Research Council (http://www.nap.edu/catalog.php?record_id=10887) defined racial discrimination as the "(1) differential treatment on the basis of race that disadvantages a racial group and, (2) treatment on the basis of inadequately justified factors that disadvantages a racial group. For the purposes of this program announcement race is defined as a continuously evolving social construct used to categorize individuals into groups that have typically been based on the physical characteristics (e.g. skin color, hair texture or other distinctive characteristics, etc.) of an individual or their ancestors. Ethnicity refers to cultural groups that have been typically defined by a common language, religion, nationality or heritage. This program announcement focuses on examining overt as well as subtle racial/ethnic discriminatory behavior and processes perceived or experienced by historically disadvantaged racial/ethnic minority groups and their contribution to persistent disparities in the receipt of quality health care and disease outcomes that have been observed among these populations.

Racial/ethnic bias is hypothesized to contribute to disparities in health through five key pathways. These include increased exposure and susceptibility to (1) economic and social deprivation; (2) toxic substances and hazardous conditions; (3) socially inflicted mental and physical trauma directly experienced or witnessed; (4) targeted marketing of potentially harmful commodities such as tobacco, alcohol and illicit drugs; and (5) inadequate or degrading medical care.

The influence of non-clinical characteristics, either actual or perceived, on provider perception of racial/ethnic minority patients might also have an impact on the health care received by patients. Physician recommendations and referrals have been shown to contribute to racial disparities in referrals for kidney transplantation and receipt of some cardiovascular procedures. Several mechanisms through which providers potentially contribute to racial/ethnic disparities in health have been suggested. These include provider bias against racial/ethnic minorities, uncertainty in their interactions with minority patients, beliefs or stereotypes regarding the health behavior of minority patients and patient response to perceived provider mistreatment or other negative racial experiences. In one report, 63% of the 76 participants in a cross-sectional survey indicated that they had experienced discrimination in their interactions with their health care provider because of their race or color. Similarly, 29% of African Americans and more than 10% of Latino/Hispanic, Filipino, and Korean respondents in the King County [Seattle, Washington] Health and Ethnicity Survey of 1995-1996 reported that they had experienced discrimination when seeking or obtaining health care due to their race or ethnicity. In interviews conducted among African Americans after the survey, perceived discriminatory experiences reported by participants included differential treatment, negative attitudes, being treated as if they were unintelligent, being ignored, inappropriate allegations and racist remarks. This highlights the importance of culturally competent relationships between patients and providers which have been defined as collaborative partnerships that facilitate successful and satisfactory delivery of care.

Experiences with racial/ethnic discrimination in the healthcare setting are not limited to patients. In a recent national cross-sectional survey, October 2006-February 2007, 60% of African-American; 33% of Asian; 17% of Hispanic/Latino(a) 42% of other race and 30% of Non-Hispanic white physicians reported the perception that patients refused their care because of their race/ethnicity. There is little empirical research however; that directly examines how patient biases towards providers affect receipt of appropriate health care.

Negative experiences in the health care setting may profoundly impact attitudes towards receiving care and influence further utilization of health care services. Data from the National Co-morbidity Study show that although African Americans had more favorable attitudes towards seeking mental health services than whites prior to using them the reverse was true after using them. Nearly 27% of African American respondents to the King County Survey reported that as a result of a discriminatory event that they were more hesitant to seek health services, 25.6% avoid the health care facility, 23.1% avoid the provider, 15.4% stopped using specific services, 10.3% avoid the personnel involved and 7.7% use services less frequently while only 25.6% did not change their behavior. Other studies have found no association between perceived discrimination and utilization of preventive health care services.

Racial/ethnic discrimination also has the potential to influence the health of racial/ethnic minorities through its association with changes in mental and physiologic states and through its influence on participation in high-risk behaviors such as excessive alcohol consumption and substance abuse. Several studies have examined the effect of racial discrimination on mental health and, in general, show that racial discrimination can be a significant source of stress for racial/ethnic minority populations and is associated with decreases in the sense of well-being including self-esteem, happiness, life satisfaction; and increased psychosis, hopelessness, anxiety, anger and substance abuse. Perceived discrimination has also been found to be associated with depression. Studies that have examined the influence of self-reported experiences with racial/ethnic bias and physiologic changes have however, provided inconsistent results. For example, some studies have shown an association between discrimination related stress and increases in blood pressure while others have not. Other research suggests that the association between perceived racial discrimination and increases in blood pressure is dependent upon coping styles. A few studies have also shown that individuals that experience discrimination and other sources of stress have a higher prevalence of chronic disease behavioral risks such as cigarette smoking alcohol and substance abuse.

This FOA specifically encourages:

  • Descriptive and analytical studies that examine racial/ethnic discrimination as a risk factor for racial/ethnic disparities in disease incidence, treatment, and outcomes;

  • The development of data resources including the identification and/or development of new data collection modalities and the evaluation of existing data collection instruments/modalities;

  • Development of innovative methods of measuring racial/ethnic discriminatory behavior, perception of exposure to racial/ethnic discrimination and novel approaches to the analysis of quantitative and qualitative data for the purpose of describing discriminatory behavior and exposure to racial/ethnic discrimination;

  • Examination of the prevalence of institutional racism in health care delivery systems or policies and its contribution to racial/ethnic health disparities;

  • The development and evaluation of interventions that enhance cross-cultural communication and reduce discriminatory behavior, the perception of exposure to racial/ethnic discrimination, and health-related consequences of racial/ethnic discrimination; and

  • Studies that examine bias/discriminatory attitudes, beliefs and behaviors that may influence/limit access to diagnostic technologies and therapies for racial/ethnic minorities, particularly in areas for which serious disparities exist such as cancer and cardiovascular disease.

  • Studies that examine the biological and psychosocial pathways that link exposure to discrimination and health.

  • All proposed studies should be sufficiently powered to provide adequate control for potential confounders including, but not limited to, gender, age, income, disability, and other factors that might explain racial/ethnic differences in study outcomes. Applicants are strongly encouraged to submit applications that go beyond simply identifying an association between race and an outcome as the sole measure of racial/ethnic discrimination. Studies that measure the prevalence, causes, and effects of racial discrimination; explanatory mechanisms that lead to discriminatory behavior, mediating factors; and processes in health delivery systems are of particular interest.

Studies should address at least one the following:

  • Employ new, novel, or innovative methods for measuring the prevalence, cause and effects of racial/ethnic discrimination/bias, explanatory mechanisms that lead to discriminatory behavior or mediating factors and processes in healthcare delivery systems;

  • Directly examine the prevalence of racial/ethnic discrimination/bias or patient perception of racial/ethnic discrimination against racial/ethnic minority patients;

  • Examine the prevalence of negative perceptions/or stereotypes that providers may have of racial/ethnic minority patients that may influence referral and/or receipt of appropriate healthcare services;

  • Examine private, governmental, or public institutional policies or practices that may negatively and disproportionately impact racial/ethnic minority receipt of appropriate healthcare services;

  • NOTE: For this FOA, The National Heart, Lung and Blood Institute (NHLBI) is only interested in receiving applications for studies that have an intervention component.

Examples of research topics and approaches that would be relevant areas of investigation under this FOA include, but are not limited to:

  1. METHODOLOGY FOR MEASURING RACIAL/ETHNIC DISCRIMINATION

    • The importance and sensitivity surrounding the topic of racial/ethnic discrimination mandates the development and utilization of measures that assure the accuracy of reported data including both construct and criterion validity. Appropriate studies include those that develop and evaluate innovative methods for measuring physician and other health care provider bias and/or use of stereotypes with racial/ethnic minority patients, patient exposure to racial/ethnic discrimination, and patient strategies used to cope with exposure to racial/ethnic discrimination in health delivery systems. With the exception of studies that examine patient perception of exposure to discriminatory behavior, studies should go beyond simply identifying an association between race and health outcomes as a measurement of discrimination. Methods for assessing the influence of patient bias towards health care providers from non-concordant racial/ethnic groups are also of interest.

  2. DISCRIMINATORY BEHAVIOR BY PROVIDERS OR OTHER STAFF IN THE HEALTH CARE SETTING

    • Studies that employ innovative methods for measuring provider attitudes, beliefs, and behaviors towards racial/ethnic minority patients including perceptions that are likely to influence recommendations, referral patterns, and receipt of appropriate care.

  3. PATIENT PERCEPTION OF THE RECEIPT OF DISCRIMINATORY CARE

    • Studies that examine factors that influence patient experiences and perception of racial/ethnically biased health care and its relationship to trust of health care providers and its influence on the future utilization of health care services including compliance with provider recommendations, delays in seeking care, and continuity in care.

    • Studies that examine racial/ethnic concordance, provider communication styles and their relationship to patient perception of the receipt of racially/ethnically biased care.

  4. INSTITUTIONAL RACISM

    • Studies that examine the impact of health delivery system practices and policies such as patient dumping, Medicare nursing care bed certification limits, privatization, closure or relocation of public hospitals, or other policies that may adversely impact the supply of racial/ethnic minority health care providers and how this might relate to racial/ethnic disparities in access to care, health status and outcomes.

    • Studies of health delivery systems, health care policies, and changes to systems and policies that have a disparate impact on racial/ethnic minorities and the roles that they might play in racial/ethnic health disparities including the utilization of health services and receipt of appropriate care by members of racial and ethnic minority populations.

    • Studies that focus on measurement of organizational factors and relationships between organizational entities such as treatment agencies and other health, social services, and criminal justice system agencies as they relate to the disproportionate use and availability of health care services among racial/ethnic minorities.

    • The role of public and institutional policies as they relate to the disproportionate use, availability or satisfaction with health care services among racial/ethnic minorities.

    • The association between racial/ethnic stigma and gaps between health care needs (e.g. treatment, prevention, and related services) and service availability.

    • The role of economic and personal costs as they relate to the disproportionate use, availability, and satisfaction with health care services among racial/ethnic minorities.

    • Studies of policy shifts (privacy policies, treatment immediacy, cost variation) in service delivery and their affect on racial/ethnic minority populations.

  5. THE EFFECTS OF RACIAL/ETHNIC DISCRIMINATION OR PERCEPTION OF DISCRIMINATION ON ON RECEIPT OF HEALTH CARE SERVICES AMONG RACIAL/ETHNIC MINORITY PATIENTS

    • Patient beliefs systems, personal biases and attitudes, and their impact on relationships with providers and on the utilization of health care services and receipt of appropriate care.

    • Patient experiences or perceptions of racially/ethnically biased health care and its influence on the future utilization of health care services and willingness to comply with physician recommendations.

    • The role of racial/ethnic stigma and discrimination on the willingness to seek health care.

    • Studies to assess the role of culture, behaviors, and attitudes on perceived racial and ethnic discrimination in the delivery and access to quality care.

    • Stereotype threat and its relationship to health care utilization.

  6. INTERVENTION STUDIES

    • Studies that test interventions designed to reduce provider bias and/or patient perception of racial/ethnic discrimination or consequences designed to ensure the receipt of quality medical care among racial/ethnic minority patients are of particular interest. Proposed interventions should be based on empirical data from adequately powered preliminary/pilot studies that support the need for and potential benefit from the specific intervention in the proposed target population.

    • Studies that assess the relationship between perceived health care discrimination and use of intervention, prevention, and treatment services.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization. All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-162.html.

NUTRITION AND DIET IN THE CAUSATION, PREVENTION, AND MANAGEMENT OF HEART FAILURE (R01): PA-11-165

Also note: Nutrition and Diet in the Causation, Prevention, and Management of Heart Failure (R21): PA-11-166 Details at: http://grants.nih.gov/grants/guide/pa-files/PA-11-166.html

Components of Participating Organizations

National Heart, Lung, and Blood Institute

National Institute on Aging

Office of Dietary Supplements

Application Receipt/Submission Date(s): Multiple dates, see announcement

Heart failure (HF) is typically a chronic disease, with progressive deterioration occurring over a period of years or even decades. Patients may become incapable of performing even the simplest activities of daily living and are at very high risk of medical complications and death. Heart failure poses an especially large public health burden. 5.8 million American adults live with heart failure. 670,000 new cases are diagnosed yearly in adults older than 45 years of age, and the average duration of disease is 8.5 years. Lifetime risk of an HF diagnosis is 20% in adults over 40. In 2006, heart failure accounted for 283,000 deaths. There were 1.1 million hospitalizations for congestive heart failure in 2004, representing $29 billion in hospital costs. It is estimated that total costs due to heart failure in 2010 will reach $39.1. Improved survival after myocardial infarction, an ever-aging population, and the rising prevalence of obesity, diabetes, and hypertension predict an increasing societal experience of heart failure that demands more effective low-cost management approaches. The influence of nutrition on HF phenotypes is poorly understood, although epidemiologic and mechanistic evidence suggests that dietary factors and alterations in myocardial nutrient metabolism may play a critical role in the development and progression of the disease. This implies that dietary modifications might reduce risk of developing HF or might delay progression to more severe forms. In addition, patients with advanced cardiomyopathies, heart muscle disorders, or congestive heart failure typically suffer from severe nutritional debilitation. Little guidance is available at present regarding optimal nutritional approaches for advanced cases, but dietary management represents a means of improving clinical outcomes for these patients.

Nutritional factors have long been implicated in the development of cardiomyopathies, particularly in animals; the veterinary and agricultural literature thoroughly documents multiple types of nutritional cardiomyopathies in species as diverse as swine, cats, dogs, foxes, rodents, and herbivores. These primarily reflect dietary deficiencies or excesses of micronutrients such as vitamins or trace elements. Nutritional deficiencies are known to cause heart failure in humans as well; the best known examples are beri-beri heart failure and Keshan cardiomyopathy, due to an interaction between Coxsackie virus and selenium/vitamin E deficiency. Other causes include viruses, genetic factors, and agents that directly promote myocardial toxicity (e.g. alcohol, cocaine, or cancer chemotherapeutic agents). Most cases of HF, however, are linked to well-known risk factors for coronary artery disease. The most striking of these is pre-existing hypertension, which appears to be both indirectly and directly linked to HF, as it is a risk factor for coronary artery disease and also is considered to result directly in the development of diastolic HF.

For relatively weak causal contributors such as diet or nutrition, a good way to obtain unbiased estimates of long-term risk is through the use of prospective cohort studies that enroll groups of healthy individuals and then track the development of disease over time. In fact, recent evidence from large, long-term follow-up studies has suggested that dietary and nutritional factors can act as effect modifiers for risk factors such as hypertension, but also may have independent and possible causal effects on HF risk. The strongest evidence to date implicates elevated body mass index, high sodium intake, and possibly elevated homocysteine levels as causal or facilitative in raising risk of HF. However, it is difficult to extrapolate cohort study findings to patient treatment approaches. For example, heart failure patients are known to have poor vitamin D status, but it is not clear whether supplementation would produce benefit. Also, relatively modest intakes of alcohol may be protective, but the mechanisms for such an effect are not defined. Improved understanding of the etiologic role of nutrition in HF, derived from hypothesis-testing research that can illuminate causal mechanisms, can be expected to lead to preventive approaches as well.

Nutrition guidance for heart failure patients is minimal, in contrast with other serious clinical cardiovascular conditions and their predisposing risk factors. Patients, families, and care providers alike seek well-integrated, robust information that accounts for specific therapeutic needs at various stages of disease, but also places them in a complete dietary context. Overall, there is a dearth of both observational and mechanistic studies related to nutrition in adult and pediatric HF patients at all stages of the disease. Thus more information is needed in various HF patient populations regarding dietary macronutrient composition, overall dietary patterns (such as the DASH diet), and the appropriate use of dietary supplements. Information particularly is needed regarding appropriate weight loss modalities for HF patients who are obese or overweight. Conversely, research is needed to better understand energy balance and nutrient metabolism and requirements in children with heart failure, who often have suboptimal growth and development patterns. Better data also are needed regarding the effects of heart failure medications on nutrient requirements and nutrient metabolism, as well as the impact of dietary modification on medication regimens. Given recent recommendations that most HF patients should engage in therapeutic exercise regimens, a better understanding is needed of the role of nutrition in exercise tolerance. For example, glycogen-sparing diets may be able to enhance exercise capacity in HF, but have not been tested widely in different patient subgroups, such as those with concurrent diabetes. Most striking, there is no evidence base at all for sodium intake recommendations for various subgroups of heart failure patients.

Advanced-stage HF patients, regardless of the original cause of disease, have unique nutritional problems that to date have been only minimally addressed. These patients typically are suffering from severe nutritional debilitation, including loss of lean body mass and energy and micronutrient reserves. Nutritional concerns among patients receiving left ventricular assist devices include a high frequency of impaired gastrointestinal function and poor nutrient absorption. Similarly, the optimal nutritional management of cardiac transplant patients is not well developed; problems include pre-transplant debilitation and post-transplant drug-nutrient interactions, which can lead to obesity, hyperhomocysteinemia, and hyperlipidemia. Better approaches are needed for characterizing nutritional status and managing nutritional support in such patients. There also is a need for a more precise definition of cardiac cachexia (based on objective endpoints), as well as research to evaluate the causes of this condition, its effects on whole body metabolism and cardiac function, and potentially useful treatments.

Investigations into delivery of nutrition-related health services are needed. Such studies could generate data that can help in decisions related to design of health care systems, effectiveness of behavioral interventions, and cost effectiveness of various treatment paradigms. Although dietary guidance often is a component of multi-disciplinary team management of HF patients, it usually is difficult to identify the specific benefits and cost effectiveness of medical nutrition therapy services compared with other treatment modalities. This is particularly important for HF patients, given that many hospitalizations are ascribed to deviations from diet and medication. Outpatients and hospitalized patients with HF need to be studied in terms of how to achieve good adherence to their prescribed treatments, and how to separate adherence vs. efficacy effects for dietary modifications. Research also is needed on cognitive, educational, behavioral, economic, psychosocial, family support, and other factors that affect the ability of HF patients to adhere to dietary recommendations.

A diverse array of investigator-initiated projects could effectively broaden the knowledge base on nutrition and HF. Studies are needed to develop and characterize novel and existing veterinary, agricultural, and laboratory small and large animal models of HF, to use in for research ranging from fundamental mechanisms to whole organism functions. Approaches that include transcriptional profiling, metabolomics, proteomics and transgenic animal models could be used to evaluate the role of alterations in nutrient metabolism on cardiac function and might shed light on the role of gene-nutrient interactions in understanding individual risk of developing heart failure, as well as predicting individual response to treatment.

Epidemiologic and population science approaches could be useful in clarifying interactions between diet, nutritional status, and risk of cardiac dysfunction/HF, and in assessing diet-disease risk relationships in patient subsets (e.g., obesity, diabetes mellitus, metabolic syndrome, anorexia nervosa, sarcopenic elderly). Use of established cohorts or existing data sets could provide an efficient research approach; taking advantage of longitudinal designs or hypothesis-generating analyses could provide descriptive data that might be the basis for power calculations for more focused studies.

The greatest impact is expected to derive from focused, mechanistically-oriented studies in humans. Such studies should be designed by multidisciplinary teams of investigators including cardiologists, nurses, and nutritionists. Most intervention trials in nutrition and HF to date have been short-term, small, and underpowered; the results have been hard to interpret, especially in the context of concurrent pharmacologic therapy, and the cardiac and nutritional endpoints often have been inadequate, preventing robust conclusions.

Appropriate designs for studies in humans would address: statistical power; effect size of the intervention; appropriate homogeneity or heterogeneity of patient populations for testing the hypotheses of interest; potential confounding factors; time course of treatment; drop-out rates; dietary intake and nutritional status assessment; treatment compliance methodology; and intermediate measurements and surrogate endpoints relevant to HF research, including biological, clinical, and behavioral responses to specific interventions.

Suitable topics for research include, but are not limited to, the following:

  • Efficacy and effectiveness of various dietary regimens and dietary patterns in the treatment of HF patients, including: effects of levels of intake of sodium, potassium, and other nutrients; how the dietary treatment of hypertension (with or without concomitant pharmacologic treatment) affects risk or clinical status indices for diastolic and systolic HF; how diet and exercise interact in HF patients; how dietary factors and nutritional status affect medication regimes in HF patients across the spectrum of disease severity; and studies of calorie restriction.

  • Identification and validation of suitable markers and indices of heart failure status as research outcomes in the context of nutrition studies and trials.

  • The role of states of energy balance and other aspects of nutritional status in relation to the onset and long-term progression of HF, including: weight loss and weight gain in patients with early and more advanced stages of HF; the diagnosis, etiology, and treatment of cardiac cachexia and other cachexic states; the role of cytokines and other biological mediators; and studies of heart failure management and outcomes in bariatric surgery patients.

  • Growth, development, nutrient metabolism, nutrient requirements, and diet-related behaviors in children with heart failure.

  • Gastrointestinal function, eating behavior, and nutrient malabsorption in HF.

  • The role of diet and nutrient intake on the risk of development or progression of HF, including effects of proportions, composition, or intake levels of macronutrients, micronutrients, or other food constituents, including non-nutritive compounds.

  • The relationships between myocardial lipid content, myocardial lipid metabolism, and cardiac dysfunction.

  • Interactions between diet, nutritional status and cardiac function, and how these interactions vary in subgroups with differing HF risk factor profiles, such as obesity and diabetes mellitus.

  • Cost-effectiveness and efficacy of nutrition-related health services, especially to identify medical nutrition therapy effects in the context of other services.

  • Factors affecting adherence to dietary guidance, including best-practice approaches to implementation of dietary recommendations by patients and families.

  • Aging-related studies including the role of nutritional or dietary factors in, or the relationship between aging-related changes in nutrient absorption and metabolism on, heart failure initiation or progression in older adults.

  • Role of diet, nutrition support regimens, and nutritional status, including metabolomic and other approaches to nutritional phenotyping, in predicting and modifying outcomes of cardiac transplantation, including on response to post-transplant drug regimens and other aspects of post-transplant management.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-165.html.

COLLABORATIVE RESEARCH IN INTEGRATIVE CANCER BIOLOGY AND THE TUMOR MICROENVIRONMENT (U01): PAR-11-146

Components of Participating Organizations

National Cancer Institute

Application Receipt/Submission Date(s): October 19, 2011

The purpose of this Funding Opportunity Announcement (FOA) is to encourage new research into the complexity of cancer by fostering new interactions with two existing and related programs within the NCI: the Integrative Cancer Biology Program (ICBP) and/or the Tumor Microenvironment Network (TMEN). The NCI specifically encourages new collaborative projects between investigators associated with the ICBP or TMEN and researchers who are not involved with the program with which they propose to collaborate. For this goal, applicants are strongly encouraged to take advantage of the multiple Project Directors/Principal Investigators (PDs/PIs) option, with at least one PD/PI representing ICBP or TMEN and at least one being currently non-affiliated investigator. The themes of these projects must be relevant to the general mission of the ICBP or TMEN. In particular, the proposed projects are expected to bring new expertise, methods, ideas, and resources to the fields of integrative cancer biology and tumor microenvironment research.

Enormous progress has been made in understanding the genetic, molecular, and cellular components of cancer. In cancer, the systems which are normally held in check by various homeostatic processes no longer function properly. It is for this reason that a basic understanding of critical cellular processes, such as cell cycle, DNA repair, apoptosis, transcription, cell migration, and matrix structure, is so critical to our understanding and treatment of cancer. However, cancer is not a disease only of cells. It is a disease of various systems and components that interact at both a molecular and cellular level to lead to initiation and progression of the disease. These interacting systems include interactions between genes in the cancer cells, between signal transduction pathways within a cancer cell, between cells in the tumor, between the tumor and its microenvironment, and between the individual and the macro-environment. Furthermore, the changing interactions of these various systems in a very dynamic environment underscore the inherent complexity of the disease. Until recently, it has been necessary to apply a reductionist approach to cancer research, focusing on a specific mutation, signaling pathway, or cell. While there has been remarkable progress in understanding each of these component parts, further integration across components or scales has been limited primarily by the lack of technology and tools needed to interrogate at any higher level.

Within the past 10 years, new technologies have been developed that have generated extensive genomic, proteomic and other genome-wide datasets. Other novel technologies have made possible vital imaging, isolation of rare cells, and organotypic culturing. Together, these developments have afforded the possibility to expand the cancer research effort to include an integrative systems approach.

To encourage and support the development of this new integrative research approach, the NCI has implemented two programs specifically targeted at addressing and examining the complexity of cancer: The Integrative Cancer Biology Program (ICBP) and the Tumor Micro-Environment Network (TMEN).

The ICBP is composed of multi-disciplinary centers focused on the development of predictive computational models of cancer which vary in the biological aspect of cancer as well as the computational or mathematical modeling approaches they are developing. Each center functions independently as well as working together on cross cutting biological and computational approaches. The program also functions as an educational and research resource for the cancer community (http://icbp.nci.nih.gov/).

The TMEN program is composed of multi-disciplinary centers focused on understanding cancer as complex disease of various cell types and environments (http://tmen.nci.nih.gov/). The overall TMEN goal is to achieve a high-level understanding of stromal composition and tumor-stromal interactions in clinically important tumor sites. In addition to high scientific productivity of individual research programs, this goal requires ensuring that results, ideas, and resources are shared freely within the Network, promoting trans-Network collaborative projects.

In the course of their research and outreach activities, the component ICBP and TMEN centers have also created a community of investigators with expertise in these emerging integrative areas and a compendium of resources that includes reagents, software, and other tools. Through this new initiative, individual investigators not affiliated are invited to collaborate with investigators affiliated with one of the programs, thereby extending the programs to a wider community.

This FOA is designed to facilitate new projects in integrative cancer biology and/or tumor microenvironment research and to extend current research conducted in the ICBP and TMEN programs through collaborations with the broader research community. Projects proposed in response to this FOA should be collaborative, and relevant to the ICBP or TMEN missions. In addition to proposing new research, these projects should leverage the resources and expertise available in the ICBP and TMEN and extend and enhance the focus of the ICBP and TMEN with new ideas, methods, expertise, and resources. A broad range of potential collaborative projects are possible. In particular, these collaborations present an opportunity for investigators with expertise in other biological systems or organ sites not currently being modeled or studied within the ICBP or TMEN centers and investigators from complementary disciplines such as applied mathematics and engineering to work with ICBP or TMEN investigators to propose new projects in integrative cancer biology or tumor microenvironment research. The proposed projects may build on current ICBP and TMEN programs and/or efforts but should not overlap.

Interested researchers, not currently affiliated with the program they are proposing to collaborate with, should consult the list of key investigators from the ICBP and TMEN programs designated by the ICBP and TMEN centers posted on the following websites:

Collaborating teams composed of at least one ICBP or TMEN PD/PI and at least one non-affiliated PD/PI are eligible to propose projects to thisFOA. Projects supported through this FOA will be affiliated with the ICBP or TMEN. Project PDs/PIs or other key personnel are invited to participate in ICBP or TMEN events relevant to the scope of their projects, including relevant ICBP and TMEN semi-annual PD/PI meetings.

Projects proposed should be new and should be aligned with the overall mission of the program, ICBP or TMEN. Below are examples of the types of collaborative research projects this FOAwould support. This list shows possible examples but is not all inclusive. Any project which is within the mission of the ICBP or TMEN and fits the other criteria outlined in this FOA will be considered.

Examples of possible ICBP collaborative projects:

  • Computational modeling of cell cycle events or other cancer relevant cellular processes in cancer vs. normal cells;

  • Adoption and modification of current modeling approaches within the ICBP to new organ sites or new cancer questions;

  • Generation and application of new mathematical or computational approaches to modeling and simulation in the study of cancer;

  • Integration of models cancer processes across temporal and spatial scales

  • Application of new technology to generate quantitative measurements for interrogation and modeling of cancer processes;

  • Experimental designs to validate and refine current ICBP models; and

  • Application of integrative approaches in the identification and testing of new therapeutic agents.

  • Examples of possible TMEN collaborative projects:

  • Characterization of the functions of and interactions among the component cells, growth factors/chemokines, and matrix molecules in normal organ and tumor-associated stroma;

  • Identification of alterations in the microenvironment which are critical for tumor development, progression, and metastasis, and elucidation of the mechanisms responsible for these changes;

  • Characterization of the role of the inflammatory and immune cells in the initiation, progression and metastasis of the tumor;

  • Identification of tumor stem or progenitor cells (and other relevant stem cells within the stroma) and characterization of the interactions between stromal cells and tumor stem cells;

  • The role of the bone marrow derive cells in tumor progression and metastasis; and

  • Development of novel technologies and model systems for the study of the microenvironment.

Eligible organizations and institutions include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For the goals of this FOA, applicants are strongly encouraged to take advantage of the multiple PDs/PIs option.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-146.html.

QUANTITATIVE IMAGING FOR EVALUATION OF RESPONSES TO CANCER THERAPIES (U01): PAR-11-150

Components of Participating Organizations

National Cancer Institute

Application Receipt/Submission Date(s): Multiple dates, see announcement

This funding opportunity announcement (FOA) is designed to promote research and development of quantitative imaging methods for the measurement of tumor response to therapies in clinical trial settings, with the overall goal of facilitating clinical decision making. Proposed projects should include the appropriate development and adaptation/implementation of quantitative imaging methods, imaging protocols, and software solutions/tools (using existing commercial imaging platforms and instrumentation) and application of these methods in current and planned Phase 1 and 2 clinical therapy trials. The proposed projects must be focused on imaging-derived quantitative measurements of responses to drugs and/or radiation therapy, and/or image-guided interventions (IGI). It is anticipated that these research goals will require multidisciplinary efforts. Therefore, this FOA encourages applications from multi-disciplinary teams to include oncologists as well as clinical and basic imaging scientists. The involvement of industrial partners in the development and adaptation/implementation of quantitative imaging methods to aid cancer therapies is not required, but is strongly encouraged.

In order to maximize the sharing of ideas and approaches to validate and standardize imaging data and related metadata for imaging-based quantitative measurements of tumor responses to cancer therapies, the awardee teams will be required to participate and collaborate in an NCI-supervised organizational structure to be called the Quantitative Imaging Network (QIN).

Regarding the clinical trial component, the FOA will support only the development and adaptation/implementation of quantitative imaging endpoints (including imaging methods and related software tools research, and/or informatics infrastructure, as needed). Eligible clinical trials may be ongoing or planned, but these trials must be funded through other sources. Therefore, no support for the clinical trials, as such, will be provided under this FOA.

In addition, in connection with FOA, the NCI will NOT support

  • The development of any tumor imaging hardware components or imaging systems; and

  • The use of prototype imaging platforms/instruments for data collection.

Investigators seeking support for imaging clinical trials, as such, are referred to the following initiatives:

Investigators seeking to validate or optimize prototype imaging hardware and methodologies for in vivo or animal studies, are encouraged to consider PAR-07-214 (http://grants.nih.gov/grants/guide/pa-files/PAR-07-214.html).

Research on early-stage imaging technology development and testing, can be supported by the traditional NIH R01 or R21 grant mechanisms.

Challenges for the quantitative assessments of therapeutic responses. Advances in molecular medicine offer the potential to move beyond traditional cytotoxic anticancer treatments and develop safer and more effective targeted therapies based on molecular characteristics of a patient's tumor. This opportunity is recognized by the NCI Clinical Trials Working Group (CTWG; http://integratedtrials.nci.nih.gov/ict/CTWG_report_June2005.pdf). However, significant translational research efforts are needed to realize these emerging opportunities. These efforts must include the development of improved imaging methods and protocols for quantitative assessments of therapeutic responses. Such quantitative assessment may require the use of multiple imaging modalities. The development of anatomical, functional, and molecular imaging methods requires proper recognition and addressing of the complexities associated with the expression of suspected biomarkers. Moreover, a full understanding of the response patterns for the potential surrogate biomarkers (e.g., those used to monitor angiogenesis, hypoxia, and necrosis) may often require the use of modeling and/or multiparametric analysis of the image data to examine quantitative correlations with other clinical metadata and clinical outcomes. These requirements generally hold for the measurements of tumor responses to drugs or radiation therapy, and image-guided interventions (IGI). Requirements for these imaging approaches to aid quantitative measurements of therapeutic response were addressed at recent NCI-supported workshops, and in related reports. Specific recommendations were formulated for measurements of therapeutic responses, using PET (positron emission tomography) and MRI (magnetic resonance imaging). These recommendations included, for example, the need for repeat measurements to determine the minimum changes that can be measured in responses to therapy in a statistically robust manner. For details, see the following links: http://jnm.snmjournals.org/cgi/reprint/47/6/1059; http://imaging.cancer.gov/reportsandpublications/ReportsandPresentations/MagneticResonance; http://www.rtog.org/; http://www.aaci-cancer.org/irats/pdfs/rider.pdf; and http://www.rthttp://www.aaci-cancer.org/irats/about_network.aspog.org/.

In addition, the increasing number of experimental oncologic therapeutic strategies has generated the urgent need to develop reliable and reproducible methods for early assessment of therapeutic responses. Addressing these needs is particularly crucial in the context of adaptive clinical trial design. Oncologists engaged in the development and implementation of clinical imaging tools and methods are often hampered by an absence of validated quantitative imaging methods.

Finally, the need for validated quantitative imaging protocols in oncology will continue to grow. For example, quantitative imaging data may be increasingly required by regulatory agencies (notably, the U.S. Food and Drug Administration (FDA; http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html) as evidence for medical utility (e.g., the efficacy of an experimental cancer drug). In addition, validated imaging approaches are typically essential to assess progression free survival (PFS). PFS data are particularly important for studies of several new targeted therapeutics expected to arrest cancer growth (but not necessarily eradicate the tumor).

Need for validation of imaging methods for the evaluation of therapeutic responses. Pertinent to any experimental therapy being investigated in a clinical trial, there is a need to develop consensus approaches for the harmonization of quantitative andstatistical methods. This harmonization must be conducted for the collection of imaging data and their analysis across collection sites and commercial imaging platforms (http://usms.nist.gov/workshops/bioimaging.htm). Various performance characteristics such as signal-to-noise ratio, contrast-to-noise ratio, and spatial or temporal resolution of different devices and modalities are often platform dependent. Moreover, the performance of these platforms may often fluctuate (reflecting possible instrument drift) during the course of therapy to be monitored. The development and implementation of appropriate quantity control methods, especially those using imaging phantoms, is thus a critical requirement. This approach often includes the use of a single, multi-functional phantom or an array of phantom designs that reflect measurements based on anatomy, specific function(s), and/or specific biomolecules. These phantoms may be either physical or computer-simulated. Both kinds are often designed and utilized to reveal temporal fluctuations in instrument performance. The phantom-based measurements and their evaluation are thus vitally important when the variability in instrument performance might approach the expected magnitude of the biological parameters to be measured as responses to therapy.

Need for clinical decision software tools. Quantitative imaging data that reflect responses to therapy and are correlated with clinical outcomes can provide an important basis for clinical decisions. In principle, the quantitative and objectively assessed characteristics derived from imaging experiments should be superior to the traditional, subjective (i.e., observer-based) assessments that often have high inter- and intra-observer variability. Further efforts are warranted to replace the subjective approaches with the objective assessments, Therefore, there is a critical need to develop and validate algorithms that can process collected imaging data to generate clinical knowledge for decision-making, and ideally automatically. Such algorithms are often referred to as clinical decision tools. These software tools usually involve the extraction of computed spatial features from images (generated by anatomical, functional, and/or molecular imaging methods) and/or the use of modeling methods that include both spatial and temporal characteristics. The algorithms typically have many interrelated parameters that need to be optimized prior to their use in specific clinical trials. This optimization is usually achieved through access to image databases that include pathological results or expert radiologist readings or other validation estimates such as comparison to simulated image sets. Used retrospectively, these validated data archives can be parsed in many different ways to create training and test data sets needed to benchmark the relative performance of algorithms and their clinical decision-making ability. Ideally, these datasets can be available as public archives to encourage development of more standardized methods for evaluation of clinical decision tools (go to http://ncia.nci.nih.gov/collections/). Finally, there is an opportunity to leverage support from industry, under a public-private partnership, to expand these databases for the purpose of more timely FDA approval and broad dissemination of clinical decision tools and related informatics infrastructure (http://www.fnih.org/partners/research_environment/IDRI.shtml).

Need for the standardization of software architecture. The performance of a clinical decision tool based on quantitative imaging often depends on the specific imaging platform for which it was created. This lack of transportability reduces acceptance of the quantitative methods and obscures validation procedures. One way to minimize this problem is to implement standardized open computer software architecture (one permitting plug and play software tools) for quantitative imaging tools. One of the main efforts to standardize all aspects of medical imaging and insure inter-operability is the Digital Imaging and Communications in Medicine (DICOM; http://medical.nema.org/dicom/geninfo/Brochure.pdf). DICOM Working Group 23, for example, is currently developing such standards to support inter-operability of software tools for data collection and analysis across different imaging platforms (http://medical.nema.org/Dicom/minutes/Committee/2004/2004-09-03/Approved_Work_Items/DICOM_Plug-ins_06.doc). The extension of the DICOM standard for application hosting, if approved, will reduce the dependence of software tools on specific platform configurations and will help accelerate the dissemination of commercial software tools that are FDA approved. It would be ideal to extend the applicability of the emerging standard to the clinical setting.

In connection with the cancer Biomedical Informatics Grid (caBIG) (https://cabig.nci.nih.gov/overview/), the NCI is currently supporting an open architecture/open source environment initiative, In Vivo Imaging Workspace (https://cabig.nci.nih.gov/workspaces/Imaging). This Imaging Workspace is based on an open architecture environment. It permits plug and play tools for image query, image annotation, and markup, including web-based validation of tools for image analysis using the caBIG. Several imaging companies are also exploring alternative proprietary software architectures that will potentially conform to the open architecture approach. This initiative is expected to aid efforts to develop standardized methods for validation of clinical decision tools and to assess their performance using publicly accessible archives.

General Scope of the Projects. Projects proposed in response to this FOA must be designed to develop state-of-the-art quantitative methods and for monitoring therapeutic responses. The proposed quantitative imaging methods should be based on imaging of responses to any form of oncologic therapy (namely drugs, radiation therapy, or image guided interventions [IGI]). Projects may span the development in the research settings, translation, and validation as needed, and incorporation of these solutions as endpoints into imaging protocols for current and planned Phase 1 and 2 trials in the clinical setting. The validation of imaging methods for the evaluation of therapeutic responses should be included. However, projects limited only to the validation aspects of imaging methods are NOT appropriate for this FOA. All of the proposed projects must include testing new or emerging imaging protocols and quantitative imaging methods in early phase trials (funded by other sources). All these solution/tools must be suitable for use as clinical decision software tools.

Ideally, the multi-disciplinary teams will be created to include both basic imaging research groups and clinical researchers (either within the same institution or from different institutions) as necessary to ensure that the appropriate experience in both early phase clinical trials and advanced quantitative imaging methods is achieved. Participants may include, for example, academic centers of excellence in computer science, medical physics or bioengineering, with specific experience in quantitative imaging methods, clinical decision software tools, and related informatics infrastructure. The clinical sites for data collection may include (but are not limited to) NCI-designated Cancer Centers, Specialized Programs of Research Excellence (SPOREs) or co-operative clinical trials group(s) that actively participate in the use of imaging methods in Phase 1 and Phase 2 therapy trials. The inclusion of industrial partners is strongly encouraged to help develop a broad consensus on the implementation of quantitative imaging methods/software tools that would be applicable across different imaging platforms.

To facilitate multidisciplinary interactions, applicants are encouraged to use the multiple Project Directors/Principal Investigators (PDs/PIs) option (see Section IV.2). If this option is used, it is expected that one of the PD/PIs will be designated as lead PD/PI. The lead PD/PI can be affiliated with an imaging researcher (basic or translational), a clinical researcher, or a researcher from industry, as appropriate.

In light of the advances being made with multimodal imaging, it is anticipated that applicant teams may propose research that incorporates quantitative imaging protocols and methods for several imaging modalities, including anatomical, functional and molecular imaging. While this is acceptable, it is recognized that focusing on a single imaging modality by a multi-site team can also be fruitful.

Research Areas. It is strongly suggested that the proposed research plan follows the strategy listed below, with the understanding that emphasis in each area may vary depending on the selection of clinical trial(s) and imaging modalities.

  • a. The identification of drug, radiation therapy, and/or IGI trials that would benefit from quantitative imaging methods and improve prognostic outcome, including the development and optimization of clinical trial protocols, specifically to implement quantitative imaging methods;

  • b. The development of quality assurance methods to test and characterize time related changes in imaging systems and IGI platforms during the course of therapy;

  • c. The development of algorithms, modeling and image simulation methods, and related databases to validate clinical decision software tools with the goal of improving the ability to measure the response of targeted tumors to therapy quantitatively. Ideally, these tools should be developed for a range of imaging methods and validated against existing public web accessible databases. The intent is to explore consensus methods for validating clinical decision tools. See Section VI. 2.A.3 regarding the function of the Steering Committee in this regard for the QIN.

  • d. The development of software architecture, designed to allow interoperability of software tools that may include open source approaches. The long-term goal should ideally include harmonizing data collection, analysis, and image display across different commercial imaging, therapy, and IGI platforms. Equivalent methods such as proprietary methods and solutions supported by industry are appropriate. All the methods proposed should ideally meet emerging NCI caBIG requirements and/or DICOM 23 requirements, if and when available.

To meet the goals of this FOA, each applicant team is expected to engage oncologists in the evaluation process to accept quantitative imaging for clinical decision making in clinical trials for appropriately targeted therapies. Examples of appropriate research goals to be accomplished by the end of year 5 of the projects include (but are not limited to) the following:

  • a. Completion of quantitative imaging studies incorporated into two or more Phase 1 and 2 clinical trials. This goal must properly address the important aspects of patient accrual and data analyses. Validation with patient outcome can take significantly longer than the duration of this program.

  • b. Improved consensus and rationalization for employing and optimizing quantitative, multi-modal, and molecular imaging methods for therapies where they are clinically useful;

  • c. Public registries and image database resources to support clinical decision making for therapies by the broader oncology community (i.e., NCI Community Cancer Centers Program [NCCCP], NIH Clinical Trial Science Awards, etc.); and

  • d. Replacement of observer or qualitative estimates of therapy response, such as the use of the RECIST (Response Evaluation Criteria in Solid Tumors) criteria.

Plans for progressive validation of these components for targeted of Phase 1 and 2 trials must also be described.

Awarded teams will be formed into a network for the purpose of sharing plans for validation and standardization of the assessment of the performance of software tools and to report clinical results in the use of quantitative imaging as a measure of therapy response. The network will be governed by a steering committee as described in Section VI 2.A.3 of this FOA.

The use of validation methods and software tools in response to this FOA must address the issue of compatibility with the NCI caBIG informatics initiative https://cabig.nci.nih.gov/). One of the goals of the caBIG (specifically, the caBIG imaging archive and workspace initiative) is to stimulate the development of open source informatics tools and open access to bioinformatics resources and data bases. These attributes should facilitate data integration and analysis over a broad range of data collection platforms covering imaging, genomic, and proteomic resources. Compatibility with caBIG components will aid investigators to consider the importance of other longitudinal biomarker data in response to therapy. This will give greater breadth to the research applicability. (https://imaging.nci.nih.gov/ncia/).

During the course of this program, the NCI may explore the possibility of creating a Public-Private Partnership (PPP) with the imaging and pharmaceutical industry communities to be mediated through the Foundation NIH (FNIH, http://www.fnih.org/). The long-term goal and rationale for this PPP would be the creation of an extended public database and related resources of image data, meta-data, and clinical outcome data collected from sites that are funded through the FOA. These resources could be leveraged through the PPP to facilitate more timely FDA approval of industry's clinical decision tools: http://www.fnih.org/.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations Other Than Institutions of Higher Education; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-150.html.

THE ROLE OF MICROBIAL METABOLITES IN CANCER PREVENTION AND ETIOLOGY (U01): PAR-11-152

Components of Participating Organizations

National Cancer Institute

National Center for Complementary and Alternative Medicine

Application Receipt/Submission Date(s): November 15, 2011; November 15, 2012

This Funding Opportunity Announcement (FOA) issued by the National Cancer Institute (NCI), and the National Center for Complementary and Alternative Medicine, (NCCAM), at the National Institutes of Health, encourages the submission of grant applications that characterize the effects of microbially generated metabolites on host cell biology. Specifically, this FOA seeks to leverage recent advances through the Human Microbiome Project Roadmap Initiative to characterize microbially generated metabolites and better understand their molecular mechanisms of action that affect host cell proliferative/apoptotic responses, cytokine production, inflammatory and immunomodulatory effects. This FOA will also encourage the conduct of human intervention studies that identify inter-individual variability among various racial and ethnic groups in the production of bacterial metabolites and determine their efficacy in cancer prevention. This research is necessary to better understand the role of dietary components in cancer etiology, prevention, and cancer health disparities to identify who might benefit from specific dietary recommendations and who might be placed at risk. One of the goals of this program will be to facilitate interdisciplinary collaborations among scientists engaged in nutrition, cancer prevention, cancer cell biology research, and cancer disparities research with those conducting studies with gut microorganisms. All applications must include multiple principle investigators with different areas of expertise such as microbiology, nutrition, cancer biology, analytical chemistry, or genetics. In addition, all investigators will be required to attend annual meetings with NIH personnel. Investigators may use either clinical or preclinical approaches.

The adult human gut contains up to 100 trillion organisms, known as the microbiota. Microbially generated metabolites from certain food components may be important mediators of both cancer protective effects and of cancer initiation and progression. Major advances in defining the quality, quantity, and physiological activity of the intestinal microbiota were precipitated by the conversion from culture-based techniques to metagenomics and through the NIH Microbiome Roadmap Initiative. The colonic microflora plays a critical role in human health and disease and has been suggested to influence cancer risk among various populations. Specific strains of bacteria have been implicated in the pathogenesis of cancer, including Streptococcus bovis, Bacteriodes, Clostridia, and Helicobacter pylori. Conversely, some strains of bacteria, including Lactobacillus acidophilus and Bifidobacterium longum, have been shown to be protective against colon cancer. Thus, this balance between "detrimental"• and "beneficial"• bacteria may have implications for cancer risk. It is increasingly clear that dietary components can significantly modify this balance via either the selective growth of specific bacteria or the effect of specific metabolic products. However, the production and biological effects of microbially generated metabolites from food components and their role in cancer prevention, etiology, and cancer health disparities have not been adequately investigated. This concept focuses on characterizing these microbially generated metabolites, determining their molecular targets, the inter-individual variation among various racial and ethnic groups in their production, their role in the maintenance or disruption of host intestinal epithelial cell homeostasis, their contribution to initiation of neoplasia, and/or their potential efficacy in cancer prevention.

One of the most abundant isoflavones in soy, daidzein, is differentially metabolized to equol and O-desmethylangolensin (DMA) by gut microflora in humans. In several studies, equol and O-desmethylangolensin have been shown to bind to human estrogen receptors "a and β with a greater affinity than the parent compound, daidzein. Furthermore, in studies that have assessed estrogen receptor-dependent transcription of β-galactosidase in transfected yeast assays, equol induced transcription to a greater extent than daidzein in yeast carrying estrogen receptor "a or β. Therefore, because equol mediates many of its biological effects by binding to the estrogen receptors, in vitro studies suggest that equol is more biologically active than daidzein.

Equol has been found to inhibit the growth of benign and malignant prostate epithelial cells in vitro at concentrations that can be obtained naturally through dietary soy consumption. Furthermore, Asians are significantly more likely to produce the metabolite equol than Caucasians and this has been associated with the lower prostate cancer incidence among Asians. Mammographic density was 39% lower in equol producers compared with non-producers. Furthermore, soy consumption increased the ratio of urinary 2-hydroxyestrogens to 16"-hydroxyestrone, another possible biomarker of decreased breast cancer risk, only in women who are equol producers. Therefore, soy consumption may lower the risk of prostate and breast cancers to a greater extent in individuals who are equol producers than in those who are not.

Dietary isoflavones have also been shown to differentially induce gene expression changes in lymphocytes from postmenopausal women who form equol compared to those who do not. In general, isoflavones had a stronger effect on some putative estrogen-responsive genes in equol producers than in non-producers. Because equol appears to mediate its cancer protective effects via binding to the estrogen receptor, these results further suggest that the capacity to form equol may be an important determinant of the responsiveness to isoflavone treatment. Additional studies are needed to clarify if a similar change in gene expression occurs in organs such as the mammary or prostate gland where soy intake tends to be associated with protection against cancer. Finally, it will be important to determine if non-equol producers will respond to dietary equol physiologically similar to what is observed in equol producers.

Bacterial Metabolism of Other Dietary Components. In addition to daidzein, several other dietary components can be metabolized by intestinal bacteria to cancer protective compounds. For example, plant lignans can be converted by the intestinal microbiota to the mammalian lignans, enterodiol, and enterolactone. Elevated plasma concentrations of enterolignans, in particular, enterodiol, were associated with a significant reduction in colorectal adenoma risk in a case control study. Enterolactone has been reported to induce apoptosis and inhibit growth of Colo201 human colon cancer cells in culture and following transplantation into athymic mice. Similarly, SW480 cell growth is inhibited in a dose- and time-dependent manner by enterolactone and enterodiol. When the lignans matairesinol and secoisolariciresinol were fed to Min mice, there were increased plasma concentrations of enterolactone and enterodiol but no inhibition of intestinal tumorigenesis. In contrast, secoisolariciresinol diglycoside concentrations in wheat bran from four selected wheat cultivars correlated with the cancer protective effects in Min mice, suggesting that secoisolariciresinol diglycoside may contribute to the cancer preventive effects of wheat bran. The reasons for these inconsistencies warrant future examination. Nevertheless, these studies suggest that bacterial metabolism of plant lignans can lead to compounds that are protective against colorectal cancer.

Similarly, preclinical studies have shown that enterolactone can reduce human breast cancer cell adhesion, invasion, migration and estrogen synthesis. While high serum concentrations ofenterolactone in humans have been associated with a decrease in breast and prostate cancer risk, the data is not overly compelling. These inconsistencies may relate to genetic differences and should be better evaluated.

An individual's genotype may influence their response to lignans. Women homozygous for the A2 allele of cytochrome P450c17" appear to benefit more from higher plasma enterolactone concentrations and a high consumption of dietary precursors than women without this allele. This also suggests that an individual's genetic background, their dietary patterns, and their microbiota interact and must be considered simultaneously for cancer prevention. A better understanding about how genetic polymorphisms influence the biological response to bacterial metabolites of bioactive food components is warranted.

Ellagic acid is a polyphenol that has been reported to possess a plethora of biological properties including antioxidant and cancer protective activities. Ellagic acid is present in many foods including strawberries, raspberries, walnuts, and pomegranates. Ellagic acid is metabolized by human colonic microflora to yield urolithins A and B. These urolthins have been shown to antagonize the growth promoting effect of estradiol in MCF7 human breast cancer cells in a dose-dependent manner. Furthermore, similar to equol, the production of urolithins, has been hypothesized to depend on the composition of the microflora of each individual because there is large interindividual variability in production. This variability was demonstrated in a human supplementation study: when 10 volunteers consumed 25 g fresh strawberries, excretion of urolithin B derivatives ranged from <1 to 6%; when they consumed 35 g of walnuts, excretion ranged from 1 to 81%; and when they consumed 300 ml of oak-aged red wine, excretion ranged from 2%-7%. Thus, the potential biological effects for this cancer protective dietary compound may also be different among individuals depending on their microflora. It has not been determined whether ellagic acid or urolithins are more biologically active for cancer prevention. It is also not known whether genetic polymorphisms in ellagic acid metabolizing enzymes (i.e. catechol-O-methyltransferase and glucuronyl transferases) might be associated with differences in ellagic acid metabolism, urolithin production and the resulting impact on cancer risk.

Metabolism by gut microflora may also influence tissue exposure to other polyphenols. This is particularly true for higher-molecular-weight polyphenols including proanthocyanidins or oxidized polymeric polyphenols, which are poorly absorbed in the proximal part of the gastrointestinal tract. These polyphenols are abundant in wine, tea, chocolate and many fruits. Ferulic acid, which is present in considerable quantities in most fruits, vegetables, and cereals, forms three major metabolites when incubated with human microbiota. These metabolites have also been found in human fecal samples and are more potent inhibitors of prostaglandin metabolism than the parent compound in vitro. The physiological significance of these microbial metabolites and whether this inhibition of inflammatory pathways contributes to a decreased cancer risk when consuming a polyphenol rich diet remains to be determined.

Gut Microbes and Obesity. Obesity has been linked with both cancer incidence and mortality. Recent work also suggests that obesity may have a microbial component. Investigators have used genetic sequencing to determine that 12 obese individuals had more Firmicutes and nearly 90% less Bacteroidetes than 5 lean individuals. Furthermore, when the obese volunteers spent one year on a low-fat or low-carbohydrate diet and lost as much as 25% of their body weight, the proportion of Firmicutes in their colon dropped and that of the Bacteroidetes rose. Similar to humans, mice that are genetically obese (ob/ob) have a higher proportion of intestinal Firmicutes and 50% fewer Bacteroidetes than their lean siblings. When germ-free mice were colonized with either the microbiota from obese (ob/ob) or lean (+/+) littermates, the mice given the microbiota from obese mice extracted more calories from their food and had a significantly greater increase in total body fat than in mice colonized with the microbiota from lean mice. These data suggest that differences in the efficiency of caloric extraction from food may be determined by the composition of the microbiota, which in turn, may contribute to differences in body weight. Future work is needed to determine whether manipulation of the gut microbial community could be an approach for the treatment and/or prevention of obesity in humans and whether this modifies cancer risk.

Transplanting the gut microbiota from normal mice into germ-free recipients increased their body fat without a change in food consumption by increasing caloric release from the diet and by modulating host genes that affect energy deposition in adipocytes including fasting-induced adipocyte factor (Fiaf). Fiaf is a circulating lipoprotein lipase inhibitor and its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. These findings suggest that the composition of the gut microbial community may affect the amount of energy that is extracted from the diet. In contrast to mice with a gut microbiota, germ-free animals are protected against the obesity that develops after consumption of a Western-style, high fat, sugar-rich diet. Their continuously lean phenotype is associated with increased skeletal muscle levels of AMP-activated protein kinase and its downstream targets involved in fatty acid metabolism such as acetyl CoA carboxylase and carnitine-palmitoyl transferase. Moreover, germ-free knockout animals lacking Fiaf are not protected from diet-induced obesity because of reduced expression of genes involved in fatty acid oxidation. Therefore, the gut microbiota can influence both sides of the energy balance equation; namely, as a factor that influences energy utilization from the diet and as a factor that affects host genes that regulate how energy is expended and stored. Future studies are needed to better understand whether the microbiota has a similar effect on energy utilization and gene expression in humans.

Specific research areas of interest include, but are not limited to, the following areas:

  • Examine metabolites of polyphenols generated by gut bacteria and determine their role in inflammation and colorectal cancer.

  • Utilize mouse models of human cancer with either a human flora or germ free for evaluating the role of soy constituents/metabolites on key cancer related processes.

  • Examine urolithin production in humans as a function of ellagic acid intake on activities and expression of cytochrome P450 and phase II enzymes in human buccal cells and esophageal tissue.

  • Evaluate the role of dietary animal fat on the population of sulfur-reducing bacteria and their production of genotoxic metabolic products such as hydrogen sulfide.

  • Define functional changes and mechanisms that demonstrate microbial product's carcinogenic effects on host cell biology.

  • Examine the ability of oral probiotic or prebiotic supplementation to modulate colon cancer initiation or progression through their effects on microbial metabolites.

  • Identify microbially generated metabolites of ginseng (Panax ginseng or quinquefolius) with documented cancer preventive activity, and sources of individual variation in generation or utilization of these metabolites.

  • Identify differences in the biological effects of microbially generated metabolites among various racial and ethnic populations that may contribute to cancer health disparities.

Eligible organizations and institutions include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; eligible agencies of the Federal Government; U.S. territories or possessions; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components on applications submitted by U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

Applicants are encouraged to consider designating multiple PD(s)/PI(s) with different areas of expertise such as, but not limited to, microbiology, nutrition, cancer biology, analytical chemistry, or genetics. Multiple PD(s)/PI(s) option may thus be used to address one of the goals of this initiative, which is to facilitate interdisciplinary collaborations among scientists engaged in nutrition, cancer prevention, cancer cell biology research, and cancer disparities research with those conducting studies with gut microorganisms.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-152.html.

BASIC CANCER RESEARCH IN CANCER HEALTH DISPARITIES (U01) PAR-11-156

Components of Participating Organizations

National Cancer Institute

Application Receipt/Submission Date(s): June 23, 2011; November 23, 2011

Through this Funding Opportunity Announcement (FOA), the Center to Reduce Cancer Health Disparities (CRCHD) and the Division of Cancer Biology (DCB), and the Division of Cancer Prevention (DCP), at the National Cancer Institute (NCI), invite cooperative agreement research (U01) grant applications from investigators interested in conducting basic research studies into the biological causes and mechanisms of cancer health disparities. These awards will support innovative mechanistic studies that investigate biological/genetic bases of cancer health disparities, including basic research in prevention studies in populations with cancer disparities. This FOA is also designed to aid and facilitate the growth of a nationwide cohort of scientists with a high level of basic research expertise in cancer health disparities research who can develop resources and tools, such as biospecimens, cell lines and methods that are necessary to conduct basic research in cancer health disparities.

This FOA will use the U01 cooperative agreement grant mechanism and runs in parallel with an FOA of identical scientific scope, PAR-09-160, which utilizes the Exploratory/Developmental (R21) grant mechanism.

Cancer health disparities represent a major public health concern in the United States. Regardless of socioeconomic factors, minority populations have higher overall incidence rates and worse outcomes than the overall population. Understanding the causes of genomic/genetic/epigenetic variability between ethnic groups that impact cancer susceptibility and/or response to therapy, is vital to reducing the observed cancer outcome gaps in this country. Several recent studies (2006-2007) suggest there may be a biological basis for the observed unequal burdens of cancer across the racial/ethnic populations. The NCI specifically encourages evidence-based mechanistic investigations of factors that are designed to increase our understanding of the biological basis of cancer health disparities.

Research applications should focus on basic cancer research and cancer health disparities, consistent with the research interests of the Division of Cancer Biology (DCB, http://dcb.nci.nih.gov/), the Division of Cancer prevention (DCP, http://prevention.cancer.gov/) and the Center to Reduce Cancer Health Disparities (CRCHD, http://crchd.cancer.gov/). The DCB supports research in the broad areas of cancer cell biology, cancer etiology, cancer immunology and hematology, DNA and chromosome aberrations, structural biology, and the tumor microenvironment. The DCP supports research that will generate new information about molecular processes that are susceptible to intervention, developing effective prevention/chemoprevention agents, discovering early detection biomarkers, pinpointing mechanistically targeted nutrients and conducting phase I, II and III clinical trials in prevention. The CRCHD supports cancer health disparity research focused on basic, hypothesis-driven studies that explicitly address the unequal burden of cancer amongst racial/ethnic minorities or other underserved populations across the cancer continuum.

For this FOA, the NCI is particularly interested in the interplay of race/ethnicity with cancer biology, such as the use of biospecimens from different racial/ethnic groups or the use of ancestral markers in determining more genetically defined measures of race and ethnicity. These awards will provide support for development and testing of new methodologies, prevention strategies, development and testing of new research technology, secondary analysis of existing data, self-contained research projects, and innovative studies that provide a basis for more extended research in cancer disparities (see also http://dccps.nci.nih.gov/smallgrants/).

Research topics of interest include but are not limited to:

  • Examination of ethnic differences in HPV strain types/infection prevalence;

  • Studies of polymorphisms in liver detoxification enzymes;

  • Examination of differences in gene expression profiles in triple negative breast tumors in African-American women;

  • Studies of polymorphism and copy number variations in key cellular processes related to cancer disparities

  • Examination of differences in gene expression profiles in triple negative breast tumors in African-American women;

  • Studies on the role of TP53 haplotypes in lung cancer among African-Americans;

  • Genetic/epigenetic susceptibility differences between ethnic populations; and

  • New animal and cell culture models/systems designed to investigate cancer disparities

  • Applications that focus exclusively on Genome-Wide Association Studies (GWAS) are not appropriate for this FOA. Applications focused on behavioral or community based studies will not be appropriate for this FOA.

  • This FOA represents the first Cooperative Agreement (U01) grant mechanism to support basic cancer research on cancer health disparities. The award will provide support for basic research projects that will develop and test new methodologies and new research technologies focused on cancer health disparities.

Eligible organizations and institutions include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-156.html.

NIDDK MULTI-CENTER CLINICAL STUDY COOPERATIVE AGREEMENT (U01): PAR-11-157

Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases

Application Receipt/Submission Date(s): Multiple dates, see announcement

As announced in NOT-DK-07-015, and clarified in NOT-DK-10-003, NIDDK will support investigator-initiated, multi-center clinical studies through a two part grant process: (1) implementation planning (U34) grant followed by (2) multi-center clinical study cooperative agreement (U01). PAR-10-197, NIDDK MULTI-CENTER CLINICAL STUDY IMPLEMENTATION PLANNING (U34) GRANTS, addresses the U34 grant; this PAR, NIDDK MULTI-CENTER CLINICAL STUDY COOPERATIVE AGREEMENTS (U01), addresses the second part of the grant process.

This policy applies to all clinical studies, interventional trials as well as observational studies, conducted at three or more centers. NIDDK will not accept applications for multi-center clinical studies that are submitted as R01s, with the exception of ancillary studies to existing cooperative agreements, which can be submitted as R01s to PAR-09-247: Ancillary Studies to Major Ongoing Clinical Research Studies to Advance Areas of Scientific Interest within the Mission of the NIDDK (R01) (http://grants.nih.gov/grants/guide/pa-files/PAR-09-247.html), or applications submitted in response to other or future NIDDK FOAs that allow multi-center applications. This policy does not apply to pilot studies. Investigators who are interested in obtaining support for pilot studies may use the R21 mechanism, through the appropriate program announcements.

Overview of the NIDDK policy for investigator-initiated, multi-center clinical studies

Part 1. Implementation Planning (U34) Grant. NIDDK will support clinical study planning (U34) grants for multi-center clinical studies. These grants are intended to support all administrative study group activities that are required in order to begin recruitment of subjects. These activities include, but are not limited to: establishing the research team, developing tools for data management and oversight of the research, defining recruitment strategies, finalizing the protocol and investigators brochure, writing of the Manual of Operations, establishing a data and safety monitoring plan, and initiating the IRB approval process. The U34 is not designed for the collection of preliminary data, for the conduct of pilot and feasibility studies to support the rationale for a clinical study, or for designing the study. The U34 application must include the proposed study design and a full protocol.

All applications for multi-center clinical studies must complete this two-part process, unless an exemption from this requirement has been obtained from NIDDK. The U34 grant will provide up to two years of support. U34 applications will be peer reviewed by special emphasis panels convened by the NIDDK Review Branch.

The product of an awarded and successful U34 will be an application to conduct the clinical study. It is expected that receipt of a U34 grant will lead to the timely submission of an application (U01) for support of the full-scale study, incorporating the elements developed under the planning grant.

Prospective applicants should note that funding of a U34 does not guarantee or imply funding for a subsequent U01 application.

Part 2. Multi-Center Clinical Study Cooperative Agreement (U01). NIDDK will accept, peer review, and consider for funding applications for investigator-initiated, multi-center clinical studies from U34 awardees only, except when an exemption from this requirement has been obtained from NIDDK. An applicant who can demonstrate that all the work required for a submission of a multi-center clinical study application has been completed may request an exemption from the prerequisite of holding a U34 award prior to submitting the U01 application.

The materials developed in the U34 phase will allow the applicant to initiate study staff training followed by study subject recruitment soon after an expedited peer review and final NIDDK approval of the clinical study application. In order not to delay the initiation of the study, the peer review and award of the grant will be completed within four months of the receipt of the application when possible. The purpose of the review of the U01 is to insure that the applicant has accomplished the milestones established in the U34 and to make sure that the scientific landscape has not changed and that the proposed study is still of scientific importance and is feasible.

The U01 application should highlight any changes to the protocol and all key decisions made during the U34 period, and should include all DSMB recommendations. The application should include a clear discussion of the power calculations and the feasibility of recruitment.

Further information regarding the U34/U01 process, including a set of frequently asked questions (FAQs) can be found at: http://www2.niddk.nih.gov/Research/ClinicalResearch/multicenterclinicalresearch.htm.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

Only NIDDK clinical study planning (U34) grantees are permitted to submit applications for clinical study cooperative agreements awards (U01), unless an exemption from this requirement has been received from NIDDK. An applicant who can demonstrate that all the work required for a submission of a multi-center clinical study application has been completed may request an exemption from the prerequisite of holding a U34 award prior to submitting the U01 application. Information on the pre-approval process is available at: http://www2.niddk.nih.gov/Research/ClinicalResearch/multicenterclinicalresearch.htm.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-157.html.

CORE INFRASTRUCTURE AND METHODOLOGICAL RESEARCH FOR CANCER EPIDEMIOLOGY COHORTS (UM1): PAR-11-167

Components of Participating Organizations

National Cancer Institute

Application Receipt/Submission Date(s): July 6, 2011, November 10, 2011, March 6, 2012, July 6, 2012, November 8, 2012, March 8, 2013, July 10, 2013, November 8, 2013

This Funding Opportunity Announcement (FOA), issued by the National Cancer Institute (NCI), invites grant applications to provide targeted infrastructure support for the core functions of Cancer Epidemiology Cohorts (CECs) and methodological research. This infrastructure can serve either the continuation of an existing CEC or the establishment of a new CEC. This FOA will support core functions for CECs currently funded through other grant mechanisms. This FOA should be used for all requests for support to continue existing CECs or to establish new CECs.

Classic CECs are organized for large observational human population studies in which groups of people with a set of characteristics or exposures are followed systematically and prospectively for the incidence of new cancers, cancer mortality, and/or cancer-related outcomes. This definition includes large cohorts of cancer patients in observational studies involving responses to therapies and short- and long-term health outcomes occurring after diagnosis. Throughout the last two decades, CEC-based studies have helped to better understand the complex etiology of cancer and have provided fundamental insights into key environmental, lifestyle, and genetic determinants of this disease. Findings from CECs are critical for risk prediction analyses and models. These findings may also serve as a basis for cancer control measures for groups and populations at risk. Evidence generated by CECs has also been useful in providing the basis for the design and testing of many preventive and therapeutic interventions. Large biorepositories established by CECs already support genomic and epigenetic studies, and are beginning to support proteomic and metabolomic studies. Further, CECs are essential to genome-wide association studies (GWAS) and replication and/or expansion of prior GWAS findings that have led and will lead to the identification of putative cancer susceptibility loci of low penetrance and high frequency, and will potentially lead to the identification of genes associated with prognosis and survival for a variety of cancers. As the genes present in these loci are identified and their functions are clarified, the prospective exposure data accumulated from CECs afford opportunities for in-depth analyses of gene-environment interactions, which will be critical for the design of public health interventions. NCI recognizes that CECs are valuable resources that benefit the entire cancer research community and, that in order to be successful as a population sciences research resource, CECs need to accrue large and varied population samples and continue to follow-up with study participants over an extended period of time.

Support is envisioned for two types of CECs through this FOA:

  • 1. CECs with at least 10,000 study participants that are capable of supporting studies to examine the effects of multiple exposures and study participants' characteristics on the risk of multiple types of incident cancers and cancer mortality; and

  • 2. Cohorts of cancer patients including at least 10,000 participants for research addressing determinants of cancer prognosis, progression, and cancer-related outcomes among cancer survivors such as cancer recurrence, development of new primaries, survival, and health conditions and chronic diseases related to the cancer, cancer-directed therapy, or its consequences.

This FOA should be used for all requests for support to continue existing CECs or to establish new CECs.

Cohorts established to assess the role of exposures in the workplace on risk of cancer (i.e., "occupational cohorts") may be appropriate for this FOA, but only if they were established to examine a broad range of exposures potentially experienced by the general public and/or genomic factors affecting cancer risk or outcomes after cancer diagnosis. Cohorts focusing primarily on cancer risks associated with exposures in the workplace are not appropriate for this FOA.

This FOA is intended to support cohorts established to identify factors that increase or decrease the risk of developing cancer or the incidence of health outcomes after cancer. Therefore, cancer surveillance activities and development and maintenance of registries of persons with particular characteristics that do not address identification of factors increasing or decreasing risk are not appropriate for this FOA.

The activities to be supported by this FOA include the establishment, maintenance, or upgrade of CECs' core functions such as recruitment, retention, and biospecimen collection. Methodological research to validate or evaluate new or existing approaches to core infrastructure functions is also appropriate. Specific core functions that can be supported for the existing or newly proposed cohorts include, but are not limited to:

  • Ongoing or new accrual of the target population, and enrollment of special populations in the catchment area;

  • Follow-up (active and passive) of enrolled participants;

  • Systematic, high-throughput assessment of genetic or other biological markers when required to interpret new research findings and when these markers are not already available on all relevant cohort study subjects (e.g., tumor hormone receptor status);

  • Validation, quality control, standardization, harmonization, and/or calibration of data across cohorts; biospecimen collection and management; and

  • Data management and data sharing activities, and administrative and communication tasks.

  • Methodologic research may include, but is not limited to research investigating the following:

  • Improved approaches to the systematic, high-throughput assessment of genetic or other biological markers;

  • Validation of exposures and health outcomes, for example, the quality of self-reported data versus medical record information, or assessment of how well a biomarker measured through non-invasive means compares to that measured in an appropriate target tissue;

  • Development and improvement of quality control (QC) and quality assurance activities related to laboratory work, data use, biospecimens, etc.;

  • Methods for biospecimen collection and management;

  • Virtual tissue repositories with metadata about available tissues across cohorts and connections to pathologic tissue image libraries.

  • Applicants responding to this FOA are expected to focus on activities that will: enable efficient planning and operation of cohorts; maximize their potential to respond to future scientific needs; enable the CECs to address cutting-edge research questions related to cancer susceptibility in human populations; and facilitate scientific collaborations across cohorts.

Note: Research projects relying on the CECs' infrastructure are NOT appropriate for this FOA. As in the past, such projects are expected to seek support through appropriate research project mechanisms (such as investigator-initiated R01 and P01 grants).

Currently, core functions of a CEC may be supported by multiple research project grants. This fragmented support is not optimal (e.g., individual research project grants may have only partially overlapping funding periods). This FOA allows for the fragmented infrastructure components of a CEC to be consolidated under a single cooperative agreement (UM1) award.

The transition to the consolidated infrastructure support may be initiated, for example, when a grant(s) that contains core infrastructure components becomes eligible for renewal. If the application is selected for funding, the overlap with other grants will be administratively adjusted.

As the awards under this FOA will use the cooperative agreement mechanism, the implementation will involve substantial involvement of NCI program staff members in various activities that are relevant to all CECs, such as data harmonization, facilitation of multi-CEC scientific opportunities, biospecimen resources optimization, and systematic assessment of molecular markers.

During the lifetime of the CEC, NCI staff will assess yearly progress toward achievement of the yearly milestones described in the application. Achievement of these milestones will be evaluated by NCI prior to releasing funding for each year of the award.

Respondents to this FOA will be required to provide and regularly update metadata about their cohort to NCI including cohort characteristics, study protocols, basic counts of study participants with various characteristics such as biospecimen availability and study variable definitions. Investigators will be expected to evaluate and document consistency of their resources across biospecimen resources, for example, consistent with NCI's Best Practices for Biospecimen Resources (http://biospecimens.cancer.gov/bestpractices) for collection, processing, and storage of future and past biospecimens.

NCI will compile metadata across cohorts and make the information available online to assist the research community in identifying potential cohorts to address specific research questions or evaluate the potential for cross-cohort studies.

Respondents to this FOA will be expected to explore the feasibility of cross-CEC data harmonization with NCI staff and other awardees through participation in working groups, consistent with the goals of this program.

Eligible organizations and institutions include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; eligible agencies of the Federal Government; U.S. territories or possessions; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components on applications submitted by U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct (i.e., pertains to a different cohort).

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the PHS398 Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-167.html.

NIAMS MULTI-CENTER CLINICAL STUDY IMPLEMENTATION PLANNING GRANTS (U34): PAR-11-169

Components of Participating Organizations

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Application Receipt/Submission Date(s): July 1, 2011, November 1, 2011, March 1, 2012, July 1, 2012, November 1, 2012, March 1, 2013, July 1, 2013, November 1, 2013, March 1, 2014

The NIAMS is committed to identifying effective approaches to address the burden of arthritis and musculoskeletal and skin diseases and disorders. Improving health through the generation of high quality data from well-designed and executed clinical trials is a high priority for the NIAMS.

A clinical trial is defined by NIH as "a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective. Behavioral human subjects research involving an intervention to modify behavior (diet, physical activity, cognitive therapy, etc.) fits this definition of a clinical trial. Human subjects research to develop or evaluate clinical laboratory tests (e.g., imaging or molecular diagnostic tests) might be considered to be a clinical trial if the test will be used for medical decision making for the subject or the test itself imposes more than minimal risk for subjects (SF424)."•

As announced in NOT-AR-11-014, published concurrently with this announcement, the NIAMS has redesigned its clinical trials program in order to support the spectrum of such studies with funding mechanisms tailored to different levels of complexity. For trials involving greater numbers of subjects or greater complexity or risk, investigators should apply for funding through a NIAMS Clinical Trial Implementation Cooperative Agreement (UM1). These larger and more complex trials require substantial planning and preparation prior to opening for recruitment, and investigators are expected to apply for a NIAMS Clinical Trial Planning Grant (U34) prior to submitting an application for the UM1 to implement the trial. The planning grant will allow an investigator to accomplish the planning activities (manual of operating procedures, FDA approvals, etc) which are often necessary for actually implementing a clinical trial; applicants for a Clinical Trial Implementation Cooperative Agreement are expected to be able to begin the trial without further planning activities when the UM1 is awarded. Investigators who have already completed planning activities either by a previously awarded NIAMS U34, R34, or other means may also submit a UM1 implementation grant, but are strongly encouraged to consult with NIAMS staff in advance. Investigators considering applying to the NIAMS for a clinical trial grant should refer to the NIAMS Clinical Trials Policy web site.

Investigators are strongly encouraged to contact their Program Officer prior to submitting applications for a U34 clinical trial planning grant or UM1 clinical trial implementation grant. Applicants are also strongly encouraged to submit a Letter of Intent (LOI) to the NIAMS before submission of an application for either a U34 or a UM1, including new and resubmission applications. Applicants are encouraged to allow enough time before the planned receipt date, particularly if there has been no prior consultation with the NIAMS about the application. LOI should be submitted to the Scientific/Research contacts listed in the FOA who will share the request with the appropriate Program Official. This program announcement, NIAMS CLINICAL TRIAL PLANNING COOPERATIVE AGREEMENT (U34), addresses the planning phase; a companion FOA addressing the second part of the process for implementing a clinical trial cooperative agreement (UM1) is also available (PAR-11-168).

Clinical research is a significant NIAMS investment aimed at answering critical questions about a particular disease or disease process. It is essential to support intervention studies to test promising new interventions with the potential to improve health practices and clinical care. Special attention must be paid to enabling these important studies to get through the administrative processes at a reasonable pace so that the conduct of the study, analysis of data, and dissemination of results are not delayed.

The NIAMS has determined that investigator-initiated, interventional clinical trials requesting NIAMS support should undergo a rigorous planning, design, and documentation phase before a decision is made to implement a study with a substantial fiscal and human investment. The implementation of a clinical trial requires extensive administrative planning (e.g., protocol finalization, manual of operations development, establishing collaborations and estimating recruitment potential) before participant recruitment can occur. The NIAMS is offering this two-part process that separates planning from subject recruitment and study implementation to provide adequate support and facilitate the timely implementation of the studies important to the mission of the institute. In addition, use of the cooperative agreement mechanism will allow NIAMS programmatic input during the early planning stages and throughout the conduct of the actual clinical trial.

The U34 planning grants will give investigators the time and funds necessary to complete detailed clinical trial planning to meet NIAMS and NIH standards and regulatory requirements. A structured planning process will allow studies to determine the optimal design strategy and to complete the administrative activities as expeditiously as possible so that the implementation phase (UM1) can start and finish the required activities within a five-year grant period.

Part 1: Clinical Trial Planning Phase (U34)

The U34 planning grant is expected to precede the submission of a clinical trial cooperative agreement (UM1) application. The U34 will provide support to complete the administrative and planning activities that are required prior to subject recruitment. These activities may include, but are not limited to: establishing the research team, identifying collaborators and clinical sites, defining recruitment strategies and collecting data on a potential pool of interested and eligible subjects that could be recruited into the study (e.g., through conducting "model recruitment"• using focus groups, questionnaires, etc), developing the protocol and clinical investigators brochure, writing of the manual of operating procedures (MOP), establishing a data and safety monitoring plan, developing tools for data collection and data management, and initiating the IRB approval process and submitting an application to the Food and Drug Administration (FDA) for an Investigational New Drug (IND) application, IND exemption, or Investigational Device Exemption (IDE), etc. Guidelines to help investigators develop a MOP and data and safety monitoring plan can be found on the NIAMS clinical research page.

The study design and protocol for the proposed trial should be presented in the U34 application in sufficient detail so that a review group can judge the feasibility of the proposed approach and the potential significance of the trial. In instances where basic protocol development can best be completed with U34 funding, the application should indicate why this is the case and indicate how the funding will be used to complete the design of the study.

The U34 is not designed for the conduct of pilot studies to support the rationale for a clinical trial or the collection of preliminary data. Please refer to (PAR-10-282), Pilot and Feasibility Clinical Research Grants in Arthritis and Musculoskeletal and Skin Diseases (R21), to submit an application for initiating exploratory/developmental research related to the prevention or treatment of arthritis and musculoskeletal and skin diseases.

Prior consultation with NIAMS staff prior to submitting the U34 application is strongly encouraged. Please refer to (NIAMS website) for details on what should be included in the Letter of Intent (LOI) to NIAMS. Letters of Intent should be submitted to the Scientific /Research contacts listed in the FOA who will direct your request to the appropriate Program Official. Applicants may want to allow enough time before the planned receipt date to give the Institute at least 10-weeks. Applications for the U34 will be peer reviewed by a standing clinical trials review committee managed by the NIAMS Scientific Review Branch.

Prospective applicants should note that funding of a U34 planning grant does not guarantee or imply funding for a subsequent application for a UM1 clinical trial. The U34 cooperative agreement will provide up to two years of support; although it is expected most will only need one year of support.

Part 2: Clinical Trial Implementation Phase (UM1)

The product of an awarded U34 planning grant that has met its milestones, as submitted in the application and as approved by the Principal Investigator and the NIH Program Official, will be an application (UM1) to conduct the clinical trial. It is expected that a U34 planning grant will lead to the timely submission of an application for support of the full-scale study which incorporates the elements developed under the planning grant. If the planning phase is not successful, an investigator may decide not to proceed to an application for the UM1 clinical trial.

It is expected that all investigators who are considering submitting applications for clinical trials (any phase) will begin by submitting a U34 application. However, an applicant may not need a U34 planning grant if all of the administrative activities relating to the start-up of the study (e.g., the U34 milestones) are complete. If a clinical trial is ready for implementation without a planning phase, and readiness is adequately supported by documentation, a UM1 application may be submitted without a preceding U34. The investigators must be ready to implement the proposed trial by the time the UM1 is to be awarded. Note that for UM1 applications which have direct costs of $500,000 or greater in any year, prior approval for submission must be obtained from the NIAMS per the NIH large grant policy. Please refer to (NIAMS website) for details on what should be included in the request to NIAMS.

All UM1 clinical trial cooperative agreement applications will be peer-reviewed, and the NIAMS will consider the results of the peer-review process when deciding whether to support the UM1 clinical trial implementation cooperative agreement.

The U34 planning grant process is designed to permit early peer review of the rationale for the proposed clinical trial and to provide support for the applicant to establish the research team, develop tools for data management and oversight of the research, define recruitment strategies, develop and finalize the clinical protocol and all essential elements of the study required for the clinical trial including all the appropriate documents.

The activities proposed in the U34 planning grant will depend on the type and complexity of the study (e.g., drug trial, surgical, or behavioral intervention). Activities supported by the U34 planning grant include, but are not limited to, the following examples:

  • Assess potential design strategies to capture the optimal intervention, dose, and target population

  • Develop a final study protocol

  • Develop a manual of operating procedures (MOP) including details, validation, and quality control for any non-standard clinical or laboratory/mechanistic testing which will be performed

  • Develop an investigator's brochure or equivalent

  • Develop consent form(s) and, if applicable, assent form(s)

  • Develop a recruitment plan including the inclusion of women and minorities, and children

  • Conduct "model recruitment"• as described in Section I

  • Obtain required Office of Human Research Protections (OHRP) assurances if not already in place

  • Satisfy all regulatory elements of the FDA

  • Initiate the IRB approval process

  • Develop a complete set of suitable documents for submission to the appropriate regulatory authorities (i.e, IND or IND exemption, or IDE application)

  • Develop a safety monitoring plan to address how risk to subjects in the clinical trial will be minimized and the process for collecting and reporting of adverse events to the appropriate regulatory bodies

  • Develop a detailed project timeline and budget for conduct and completion of the clinical trial including funding for orderly close-out of clinical sites and preparation of a final study report

  • Identify collaborators and clinical site(s), which may include negotiating sub-contracts

  • Develop training materials and training/certification plans for study staff who will carry out the study

  • Negotiate agreements with industry, as needed, to provide drugs, devices, or other resources

  • In the event of an award, the NIAMS and the PD/PI will agree on a list of milestones to be completed during the U34 project period. They are derived from the specific activities that need to be completed before an implementation trial can be initiated. The submission of the application for the UM1 may be one of the milestones and may precede the end of the U34. The milestones will be incorporated into the notice of grant award (NoA).

Eligible organizations and institutions include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal; governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

While not required, the NIAMS strongly encourages applicants to consult with Program staff prior to resubmission.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-169.html.

EARLY-PHASE CLINICAL TRIALS FOR BLOOD CELL THERAPIES (R01): PAR-11-204

Components of Participating Organizations

National Heart, Lung, and Blood Institute

Application Receipt/Submission Date(s): October 5, 2011, October 5, 2012; AIDS Date: January 7, 2012, January 7, 2013

This FOA issued by the National Heart, Lung, and Blood Institute, National Institutes of Health, encourages Research Project Grant (R01) applications from institutions and organizations proposing to conduct early-phase clinical trials- i.e., first-in-human, phase I, or phase II trials- to evaluate innovative and novel cell therapies to treat blood diseases and/or to improve the outcome of hematopoietic stem cell transplantations. To promote this endeavor, applications that include clinical protocols and investigators will be encouraged to apply for dedicated NHLBI cell therapy resources to help them in the planning and/or conduct of the clinical trial.

Accelerating hematopoietic stem cell transplant recovery and avoiding toxicities are key issues essential to expanding transplant use and treatments for benign hematological diseases (e.g., aplastic anemia, sickle cell disease, and thalassemia). Preclinical studies have provided new strategies but to advance the field, the relevant scientific and medical questions must be addressed through clinical investigation. Early clinical studies- first-in-human, phase I, or phase II trials-are required to address these scientific and mechanistic questions and to move the field forward.

A number of issues have been seen as roadblocks hindering the clinical development of new cell therapies. Investigators with preclinical findings have found that the standard NIH grant mechanism for hypothesis-driven basic research may not be suitable for clinical questions. Also standing study sections may not include clinical expertise relevant to new cell therapies. And basic research investigators may lack the clinical trial expertise needed to address regulatory issues, early-phase clinical trial design, trial management, or statistical issues.

This FOA provides a specific opportunityfor the submission of early-phase clinical trials for novel cell therapies to treat blood diseases and/or to improve the outcome of hematopoietic stem cell transplantation.

Basic researchers that may lack clinical experience are strongly encouraged to ask for assistance from three NHLBI resource programs: the Production Assistance for Cellular Therapies or PACT, the Gene Therapy Resource Program or GTRP, and/or the Science Moving towards Research Translation and Therapy or SMARTT. In addition to furnishing important key clinical-grade resources such as cells, vectors, or biologics, the coordinating centers of these programs can provide cell regulatory support, as well as data collection and statistical support related to the use of these resources in early phase clinical trials.

Investigators planning trials and developing clinical protocols for cell therapy applications to this FOA are encouraged to consult the coordinating centers at these resource programs (links to each resource program listed below) as well as the NHLBI program staff listed in this announcement (see Scientific/Research Contact(s) in Section VII. Agency Contacts.

PACT (http://www.pactgroup.net/) is an ongoing NHLBI cell processing resource program that has been producing clinical-grade cell products for over five years. PACT facilities have been recently expanded from 3 to 5 cell production facilities. Investigators without expertise in the scale up or production of clinical-grade cell products can consult PACT experts regarding cell production protocols and proposed clinical cell therapy trials. Investigators planning clinical studies can submit applications and, if approved, obtain cells required for pre-IND studies as well as GMP-grade cells for clinical trials. The PACT coordinating center can also provide regulatory support, data collection support, and statistical support related to its cell products. If PACT centers cannot produce a specific cell product or the desired cell type cannot be shipped to the trial site, other cell processing facilities may be used.

Cell therapy trials that include gene transfer studies should consult GTRP (http://www.gtrp.org/). This resource program provides: (1) large- and small-scale viral and non-viral vectors for preclinical studies and performs immunology testing, (2) clinical-grade adeno-associated virus (AAV) vectors for use in clinical studies and GMP process-comparable AAV vectors for use in pharm/tox studies, (3) clinical-grade lentiviral vectors for use in clinical studies and GMP process-comparable lentivirus vectors for use in pharm/tox studies. In addition, GTRP can perform (4) toxicology testing and bio-distribution studies of vectors in large and small animal models as a prerequisite for use in clinical studies and its coordinating center can provide (5) regulatory support.

Clinical-grade biologics, non-biologics, and small molecules can be furnished by the SMARTT program (http://www.nhlbi.nih.gov/new/SMARTT.htm). Pre-clinical and clinical development requires materials manufactured using standard operating procedures and carefully controlled conditions to comply with Good Laboratory Practice (GLP) and current Good Manufacturing Practice (cGMP). SMARTT provides resources through four facilities: (1) a production facility for biologic therapeutics, (2) a production facility for non-biologic and small-molecule therapeutics, (3) pharmacology and toxicology center, and (4) a coordinating center.

Investigators are encouraged to work with the staff at the coordinating centers for these three resource programs to create an appropriate preclinical and clinical development plan to support the submission of a well-designed study protocol. Consistent with the trial proposed, information on the following should be included: 1) preliminary data on the use of the proposed cell type, 2) safety and efficacy data, 3) potency assay data, 3) monitoring for immune reactions, 4) data supporting trial feasibility, 5) the suitability and availability of the proposed patient population, and 6) a data and safety monitoring plan including identification of specific personnel to monitor adverse events, and proposed stopping rules. The proposed clinical protocol and consent forms are submitted in the appendix of the application. Information on the protocol must also be provided in the research strategy section of the application including an overview of the state of the science, current status and relevance of the trial, a discussion of the specific protocol, and the approach to data collection and analysis. In the Research Strategy section, a protocol should include sections on the hypothesis, specific aims, background, eligibility criteria, treatment plan, primary and secondary outcomes, study design with accrual targets based on the statistical power of the study, number of accrual sites required based on patient availability, timeline including site start-up, patient accrual, follow up, data collection and analysis, and the data and safety monitoring plan. Certification of IRB approval for the proposed clinical protocol will not be required prior to review or prior to award. However, protocols submitted need to be well developed with the necessary regulatory and other approvals in place so the clinical trial can be initiated after award. Applicants will be expected to complete the requirements for regulatory filing, e.g., an Investigational New Drug (IND) application or Biologics License Application (BLA), prior to award and the status of discussions with the FDA should be documented in the application. Applicants need not have their clinical protocols reviewed by a Scientific Review Committee - also known as a Protocol Review Committee - at their institution prior to submission, however, since approval by this Committee is needed prior to award, the clinical protocol should be well developed at the time of application submission.

Preclinical research studies have provided advances that should be explored to determine their clinical applicability. For example, preclinical studies indicate that to increase cord blood use, insufficient cell numbers may be expanded using notch ligands. Preclinical data also indicate that cord blood engraftment can be improved using prostaglandin PGE2 or dipeptidylpeptidase-IV inhibitors. Other studies suggest that virus-specific cytotoxic T-cells may treat opportunistic infections and regulatory T-cells may control graft versus host disease or GVHD. Another example is the use of mesenchymal cells that may suppress immune responses to control GVHD or may also be useful as an adjunct to promote stem cell engraftment. Before these results might find clinical application, early clinical studies are required to address scientific and mechanistic questions and move the field forward. Depending on the stage of development, first-in-human or a Phase I trial may be needed or the clinical project may be appropriate for a Phase II study.

The objective of this FOA is to accelerate translation of new preclinical stem cell and cell therapy research advances into new cell therapies to treat blood diseases and/or to improve the outcome of hematopoietic stem cell transplantations. These first-in-human, phase I, phase II, or phase I/II clinical trials will investigate new cell therapy methods and could include testing new cell types, differentiation protocols, or other strategies.

This initiative seeks applications that consider new cell therapies for blood diseases and cell therapies adjunct to hematopoietic stem cell transplantation. Applications using minimally manipulated cell therapy products (see FDA Guidance documents on minimally manipulated products at: http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/default.htm) should consider PA-10-067 (Parent R01) or other FOAs as appropriate.

Appropriate ideas include but are not limited to the following topics:

  • Treat graft vs. host disease (GVHD) or increase immune reconstitution with regulatory T cells

  • Prevent post-transplant relapse using chimeric antigen receptors (CARs)

  • Provide safe blood cell products for transfusion applications using signaling molecules, cytokines, or transcription factors to expand blood cell populations

  • Treat monogenic blood diseases, e.g., sickle cell disease, severe combined immune deficiency (SCID), or β-thalassemia, using improved genetic vectors for hematopoietic stem cells

  • Use mesenchymal stem cells (MSC) to treat GVHD or as stem cell adjunct to improve engraftment

  • One area of potential overlap within hematopoietic stem cell transplantation will be cell therapies for the treatment of malignancies. NIH referral guidelines will be used to determine which applications are appropriate for NHLBI and which are appropriate for other NIH Institutes, e.g., the National Cancer Institute. The above list provides examples of early-phase cell therapy trials applications appropriate for NHBLI. However, prior to preparing or submitting an application to this announcement, potential applicants are strongly urged to first discuss their clinical trial application with the NHLBI program staff listed in this announcement (see Scientific/Research Contact(s) in Section VII. Agency Contacts.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-204.html.

ALCOHOL EDUCATION PROJECT GRANTS (R25): PAR-11-205

Components of Participating Organizations

National Institute on Alcohol Abuse and Alcoholism

Application Receipt/Submission Date(s): Multiple dates, see announcement

Broad ranges of educational approaches are included within the context of this FOA. Individual applications are expected to focus on the alcohol education area of Health Professions Education. This area of activity includes projects designed to support the science of dissemination of new knowledge acquired through alcohol research to a wide array of health professionals, both individuals currently practicing their professions and those in training for health professions. A broad definition of health professions is adopted, to include but is not limited to: social workers, occupational therapists, nurses, physicians, dentists, psychologists, pharmacists, counselors, and others involved in areas of physical, mental, and/or behavioral health services where target groups experience alcohol use disorders. Appropriate activities may include, but are not limited to, the development of courses, programs, curricula, and related materials designed to educate scientists, educators, service providers, and others about scientific advances in our knowledge of alcoholism, alcohol abuse, and alcohol-related problems (e.g., health-related complications with individuals who have diabetes and consume alcohol), and improve science literacy in this area. Activities and projects should attempt to meet the following criteria: 1) applicants are strongly encouraged to include members of the target health professions audience as consultants or in the planning process; 2) educational intervention innovations and materials should be adoptable and adaptable by educators in health profession training settings other than those where they have been initially pilot tested; 3) educational innovations should address relevance and relatedness to current and/or emerging standards for education in the target profession; 4) evaluation components must address outcomes and be conducted using appropriate types of research designs, instrumentation, procedures, sampling strategies, and plans for analyses; and 5) products developed under this mechanism may be shared with NIAAA for use and dissemination through its website, workshops, trainings, conferences, and presentations.

This (FOA) encourages applications from applicant organizations that propose creative and innovative Health Professions education programs in the mission area(s) of the NIAAA. The NIH Education (R25) grant mechanism is a flexible and specialized mechanism designed to foster the development of biomedical, behavioral, and clinical researchers through creative and innovative research education programs. The NIH encourages all proposed programs to foster the participation of individuals from racial and ethnic groups underrepresented in biomedical and behavioral research, individuals from disadvantaged backgrounds, individuals with disabilities, and women.

The proposed education research program may complement other, ongoing research training and education occurring at the applicant institution, but the proposed educational experiences must be distinct from those research training and research education programs currently receiving federal support. The R25 is not a substitute for an institutional research training program (T32) and cannot be used to circumvent or supplement Ruth L. Kirschstein National Research Service Award (NRSA) mechanisms.

Eligible organizations and institutions include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date.

The sponsoring institution must assure support for the proposed program. Appropriate institutional commitment to the program includes the provision of adequate staff, facilities, and educational resources that can contribute to the planned program.

Institutions with existing Ruth L. Kirschstein National Research Service Award (NRSA) institutional training grants (e.g., T32) or other Federally funded training programs may apply for a research education grant provided that the proposed educational experiences are distinct from those training programs receiving NIH support. In many cases, it is anticipated that the proposed research education program will complement ongoing research training occurring at the applicant institution.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Prog Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

The PD/PI should be an established investigator in the scientific area in which the application is targeted and capable of providing both administrative and scientific leadership to the development and implementation of the proposed program. The PD/PI will be expected to monitor and assess the program and submit all documents and reports as required.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Applications must describe the intended participants, and the eligibility and/or specific educational background characteristics that are essential for participation in the proposed research education program. Identify the career levels essential for participation in the planned program.

Unless strongly justified on the basis of exceptional relevance to NIH, research education programs should be used primarily for the education of U.S. citizens.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-205.html.

PILOT STUDIES TO DEVELOP AND TEST NOVEL, LOW- COST METHODS FOR THE CONDUCT OF CLINICAL TRIALS (R01): RFA-HL-12-019

Components of Participating Organizations

National Heart, Lung, and Blood Institute

Application Receipt Date(s): October 13, 2011

This initiative supports the development and testing of novel, low-cost methods of conducting clinical trials of interventions designed to reduce morbidity and mortality in patients with diseases of interest to NHLBI. New and innovative designs that have not been tested in previous studies but hold potential for increasing the efficiency and reducing the cost of conduct of clinical trials are especially encouraged.

Results from clinical trials are among the strongest type of evidence for medical decision making. However, the current paradigm for conduct of most clinical trials involves the establishment of specialized clinical sites and staff for recruitment of participants and delivery of the intervention, data coordinating centers to receive and analyze data, and the transfer of information through dedicated electronic data entry systems. Clinical information necessary for study outcome is obtained through special visits by participants or through the retrieval of existing clinical records, extraction of information from the records and re-entry into a new database. This last step may also include the adjudication of clinical events to determine if they meet study criteria. This infrastructure results in trials that are expensive and burdensome to conduct.

In addition to the infrastructure, there are several other barriers to the conduct of clinical trials. The process for obtaining human subject approval by institutional review boards can be time consuming, and items required for approval vary between boards. Inadequate time within the clinic to implement protocols and the need for research studies to fit into clinical workflow has also been identified as a barrier to research in the primary care setting. Low enrollment of eligible participants delays the start and endangers the completion of many clinical trials.

The recent push to determine the most effective interventions for patients has intensified the need for more efficient methods to conduct clinical trials. The existing paradigm may be appropriate for trials that involve high-risk interventions, early phase studies, or stringent inclusion/exclusion criteria. However, more trials are needed that compare known, approved interventions including drugs, behavior change, surgical interventions, or systems change to determine the most effective. To be useful to consumers and health care providers, these studies must be widely applicable, efficient so results are quickly known, and low cost so that limited resources can be used to answer a broad array of questions. The current clinical trial design does not often meet those goals. New study designs are needed.

The purpose of this FOA is to challenge investigators to design new methodologies for the conduct of clinical trials and then test the proposed methods in a clinical trial. Studies funded under this FOA are focused on development of new methods for the conduct of randomized controlled clinical trials. If the methods prove successful, ideally they would be disseminated to the larger research community and utilized in future clinical trials. Please note that NHLBI has no obligation to fund future clinical trials which utilize these methods, nor are the recipients of grants from this FOA obligated to utilize the methods in future submissions to NHLBI. Successful applicants to this FOA will propose a design that overcomes the following challenges:

  • Minimize specialized infrastructure developed solely for conduct of the clinical trial.

  • Minimize visits designed solely for the purpose of retrieving measurements for the trial.

  • Explore novel methods of obtaining patient consent that minimize the need for specialized clinical trial staff and participant visits while still meeting ethical and legal requirements.

  • Employ low-cost methods of monitoring study conduct such as adherence.

  • Test the feasibility of the design in a clinical trial.

  • Each of the challenges above may have a differential effect on the efficiency and conduct of the trial. To help elucidate the impact each change may have, investigators are required to collect operational information during the conduct of the pilot trial and assess the relative contribution of each to the improved efficiency of the clinical trial. Investigators are encouraged to utilize a team approach to better accomplish this objective with expertise in clinical trials, systems engineering, bioinformatics, computer programming as well as disease experts.

  • While development of the study design may constitute a portion of the grant, investigators must also conduct a clinical trial that utilizes the proposed design to demonstrate feasibility. These trials should be a true test (there is true uncertainty about which is the best option) but can test any appropriate intervention including drugs, behavior change, surgical interventions, or systems change. Disease conditions should be relevant to NHLBI. While investigators should attempt to have outcomes that are important to patients or health care providers (mortality, morbidity, quality of life), the relatively short duration of the FOA may require the use of surrogate outcomes in some instances. If surrogate endpoints are utilized as the outcome, these should be widely accepted as valid for the clinical condition. Finally, the trials must maintain key features of high-quality clinical trials (standardized inclusion/exclusion criteria; randomization into at least two groups; allocation concealment where possible [at a reasonable cost]; documented delivery of the intervention and where appropriate, standardization of the intervention; objective assessment of outcomes that is equivalent by study group).

  • To facilitate interaction between study teams, a 2 day meeting of grant recipients will be held in Bethesda in year 1 and year 4 of the grant.

  • Guidance for Applicants

  • Applicants should address each of the following:

  • Applicants are encouraged to address each of the first four challenges above in their study design. In cases of multiple applicants with similar competitive scores, applications that address multiple challenges will be given higher priority.

  • While development of the study design may constitute a portion of the grant, investigators must also conduct a clinical trial that utilizes the proposed design to demonstrate feasibility. Trials must be a true test and have outcomes relevant to patients and clinicians. Surrogate or intermediate outcomes are acceptable if the proposed measures are widely accepted as valid.

  • Applications that do not include this will be considered unresponsive.

  • Investigators must determine the reliability and the validity of the data collected during the trial. For example, if the research team is utilizing blood pressure measurements from an electronic health record, they must validate the accuracy of those measurements during the planning or execution of the trial.

  • Studies that seek to determine methods to combine electronic medical records from multiple sources are encouraged, as are studies that utilize the CTSA resources.

  • Investigators are encouraged to propose designs that overcome these challenges in a manner that is generalized to a variety of diseases and clinical questions. Applications that propose solutions that are targeted at a specific clinical question will not be considered unresponsive. However, in cases of multiple applicants with similar competitive scores, a solution generalized to a large range of diseases or interventions may be used in determining the order of funding.

  • Applicants should budget for 2 of their study team members to attend a 2-day meeting to be held in Bethesda in year 1 and year 4 of the grant. This meeting will be an opportunity to share strategies and results.

Examples (but not limited to) of new design features:

  • Development of a method of randomization that is embedded within the electronic health record.

  • Development of a method of participant consent that is brief and embedded within the electronic medical record while still meeting legal and ethical requirements.

  • Development of a method to consent participants in a group format while still meeting legal and ethical requirements.

  • Development of a method to utilize electronic health records to obtain study outcomes that is valid, complete, and easily generalized across a range of electronic health record systems.

  • Development of a method to utilize and compensate health care providers to identify, recruit, and randomize eligible participants during routine clinic visits.

  • Development of a method to administer study interventions as part of routine clinical care by health care providers.

  • Development of internet based studies with all study related activities occurring via the internet including recruitment, randomization, consent, and follow-up.

  • Development of cluster randomized trial methods for testing system-based interventions.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Applicants must include a plan to assess the relative contribution of each design change to the improved efficiency of the clinical trial. Applications that do not include this will be considered unresponsive. Applicants must include a plan to determine the cost per participant to conduct the trial. Applications that do not include this will be considered unresponsive.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-019.html.

NIMHD HEALTH DISPARITIES RESEARCH (R01): RFA-MD-12-001

Components of Participating Organizations

National Institute on Minority Health and Health Disparities

Application Receipt Date(s): June 14, 2011

Although scientific and technological discoveries have improved the overall health of the US population, racial/ethnic minority populations (African Americans, Hispanics/Latinos, Asian Americans, American Indians/Alaska Natives, Native Hawaiians and other Pacific Islanders), socioeconomically disadvantaged populations, and rural populations continue to experience a disproportionate burden of disease. Increased morbidity, mortality, incidence of disease, disability, and adverse outcomes in cancer, cardiovascular disease, diabetes, HIV/AIDS, infant mortality, and other conditions are well documented in the scientific literature. Moreover, there are a range of health conditions that have yet to be studied adequately in these health disparity populations.

As the Nation's steward of biomedical and behavioral research, NIH has devoted considerable resources to characterizing the root causes of health disparities. As a result of these efforts, a complex and multi-factorial web of interconnected and overlapping factors (i.e., biological, behavioral, environmental, and societal) has emerged. As an important next step, research is needed that capitalizes upon this knowledge about causal pathways to directly and demonstrably contribute to the elimination of health disparities.

Investigators who conduct original and innovative basic biomedical, social, behavioral, clinical, or population-based research directed toward eliminating health disparities are invited to apply to this FOA. Projects must include a focus on addressing disparities in disparity populations as a whole, a single health disparity population, or a subgroup within a health disparity population. Projects addressing the improvement of health in racial/ethnic minority populations (without a specific emphasis on disparities relative to other groups) are also accepted under this announcement.

Applications should provide a clear link between the proposed work and the improvement of minority health and/or the elimination of health disparities. Applications focused on diseases or conditions more prevalent or associated with greater morbidity/mortality in one or more disparity populations, without the proposed work itself being focused on minority health or health disparities, are discouraged.

Research aims may include, but are not limited to, biological mechanisms; behavioral strategies; lifestyle factors; environmental, structural, and economic factors; cultural and family influences; delivery system interventions; medical procedures and regimens (including alternative therapy), and medical assistive devices and health information technologies. Projects may involve primary data collection or secondary analysis of existing datasets.

Research topics of specific interest include but are not limited to:

  • Studies of health conditions associated with significant mortality or disability that has not been adequately studied in health disparity populations (e.g., focal glomerulosclerosis, lupus and other autoimmune disorders, pancreatic disorders, periodontal disease, and traumatic brain injury).

  • Intervention studies that involve multiple population groups and/or evaluate the effectiveness of culturally-tailored interventions across different population groups.

  • Analysis of local, state, or national health policies that increase or reduce health disparities.

  • Studies of health information technologies to improve health literacy and/or increase access to healthcare.

  • Interventions to improve cultural competence of providers that demonstrate a clear link to improvement in patient outcomes.

  • Research projects that directly measure the impact of project activities on levels of health disparities across population groups are strongly encouraged.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-MD-12-001.html.

PREDICTIVE MULTISCALE MODELS FOR BIOMEDICAL, BIOLOGICAL, BEHAVIORAL, ENVIRONMENTAL AND CLINICAL RESEARCH (INTERAGENCY U01): PAR-11-203

Components of Participating Organizations

National Institute of Biomedical Imaging and Bioengineering

Department of Energy

Food and Drug Administration

National Cancer Institute

National Center for Research Resources

National Human Genome Research Institute

National Heart, Lung, and Blood Institute

National Institute on Aging

National Institute on Alcohol Abuse and Alcoholism

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Drug Abuse

National Institute of Environmental Health Sciences

National Institute of General Medical Sciences

National Science Foundation

Office of Behavioral and Social Science Research

Application Receipt/Submission Date(s): June 17, 2011, September 27, 2011, January 31, 2012, May 31, 2012, September 27, 2012, January 31, 2013, May 31, 2013, September 27, 2013, January 31, 2014

The goal of this interagency funding opportunity announcement is to support the development of multiscale models to accelerate biological, biomedical, behavioral, environmental and clinical research. The NIH, DOE, FDA, and NSF recognize that to efficiently and effectively address the challenges of understanding multiscale biological and behavioral systems, researchers will need predictive, computational models that encompass multiple biological and behavioral scales. This FOA also encourages the development of new, non-standard modeling methods and experimental approaches to facilitate multiscale modeling.

Multiscale modeling uses mathematics and computation to quantitatively represent and simulate a system at more than one scale while functionally linking the mathematical models across these scales. This FOA is focused on biological and behavioral scales, which include atomic, molecular, molecular complexes, sub-cellular, cellular, multi-cell systems, tissue, organ, multi-organ systems, organism/individual, group, organization, market, environment, and populations. Multiscale models of biological and behavioral systems can be used as important tools to address a range of biomedical, biological, behavioral, environmental, and clinical problems. Multiscale modeling and analysis methods inherently provide a fundamental infrastructure for understanding and predicting biological and environmental processes; diseases; and human and organizational behavior patterns and outcomes.

In 2004 the Interagency Modeling and Analysis Group (IMAG) released the Interagency Opportunities in Multiscale Modeling (MSM) in Biomedical, Biological, and Behavioral Systems Initiative, which laid the foundation for multiscale modeling by supporting grants that develop the mathematical and computational interfaces between biological scales (http://www.nsf.gov/pubs/2004/nsf04607/nsf04607.htm). In 2007 IMAG released the Predictive Multiscale Models of the Physiome in Health and Disease FOA to promote the development of multiscale models at higher levels of the physiome that are predictive of health and disease (http://grants.nih.gov/grants/guide/pa-files/par-08-023.html). In 2010, the IMAG Futures Report produced a systematic assessment, at multiple biological scales and across multiple biomedical fields, the extent to which computational modeling has made an impact in the broader biomedical research endeavor, http://www.imagwiki.org/mediawiki/images/b/b5/IMAG_Futures_Report.pdf. The current FOA reissue from IMAG promotes both the development of novel multiscale models and methods, and multiscale physiome modeling; in addition to the development of targeted partnerships to increase the impact of multiscale models in basic and translational biomedical, biological, behavioral, environmental and clinical research.

The original MSM initiative gave rise to the Multiscale Modeling (MSM) Consortium which is composed of several working groups focusing on scientific and computational issues related to multiscale modeling. The MSM Consortium has now grown beyond the original grantees of the original initiative and serves to bring together a community of modelers interested in multiscale modeling of biomedical, biological and behavioral systems (http://www.imagwiki.org/mediawiki). In addition IMAG (http://www.nibib.nih.gov/Research/MultiScaleModeling/IMAG) continues to bring together many agencies interested in multiscale modeling. The spirit of IMAG is to promote the development of new or novel modeling and analysis methods throughout the scientific community. Through the MSM Consortium, IMAG promotes collaborative team science and the sharing of good quality scientific modeling and analysis tools as a result of employing appropriate software engineering practices.

Multiscale models can be designed to integrate diverse data, create testable hypotheses leading to new investigational studies, identify and share gaps in knowledge, uncover biological mechanisms, or make predictions about clinical outcome or intervention effects. These models can draw on a variety of data sources including relevant physical, environmental, clinical and population data. Ultimately multiscale models and the information derived from their use will enable biomedical, biological, behavioral, environmental and clinical researchers to understand complex biological and behavioral systems in a manner not possible through traditional research methods. The ultimate goal of the models would be to make realistic scientific predictions to address problems and issues in the environment; in the human body (e.g., to prevent, diagnose and treat the diseases or aberrations in normal development, and/or to predict treatment outcomes); and among individuals, groups, and within populations.

For this FOA specific topics of interest include, but are not limited to, those listed below:

  • addressing compelling biological, biomedical, behavioral, environmental and clinical problems that require multiscale models to bring together different spatial and temporal scales within a specific field

  • next generation multiscale models that integrate between different fields (e.g. cardiovascular and neuroscience) and predict integrated functions

  • novel methods to fuse data-rich and data-poor scales to enable predictive modeling

  • novel methods to fuse biological and/or behavioral processes and mechanisms to model outcomes as a result of various interventions

  • useable and reusable multiscale models that will be integrated and adopted into model-poor fields (e.g. tissue engineering, regenerative medicine, drug and gene delivery, preventive interventions)

  • multiscale models strongly coupled with standardized protocols for model-driven data collection

  • implementing virtual clinical trials with multiscale models to predict outcomes

  • problem-driven multiscale models that require high performance computing (see below for available advanced computational resources)

  • model predictions that drive a community of experimentalists towards systematic testing and validation

  • predictive multiscale models that strongly incorporate uncertainty quantification

  • mechanistic multiscale models that bridge to the population level to capture more clinical and biological realism for the population

  • stochastic multiscale models that characterize interactions between individual-level behaviors and group-, market-, or population-level outcomes

  • models to explore underlying mechanisms of individual-, community-, or population-level preventive or therapeutic interventions

  • predictive multiscale models to improve clinical workflow, standard operating procedures, patient-specific modeling for diagnosis and therapy planning

  • In addition, this FOA seeks to achieve the scientific goals by encouraging highly interactive partnerships that strongly integrate truly diverse expertise to further increase the impact of multiscale models in the broader research and policy community. This list is not complete and is not limited to the following:

    • a. experimental and modeling expertise, so that the models create testable hypotheses leading to new investigational studies, or

    • b. mathematical and or statistical expertise with domain-modeling expertise, so that new methods enhance the function of the models, or

    • c. expertise focused on different spatial or temporal scales, or different experimental and observational scales, or different deterministic and statistics-driven scales, or

    • d. expertise from mature modeling disciplines with expertise from disciplines with an emerging use of models, or

    • e. expertise from different biological and behavioral modeling subfields; such as, computational neuroscience, systems biology, physiome research, agent-based modeling, system dynamics, and microsimulation.

As described in Section IV.2 (Research Plan) the application must include: 1) Partnership Plan to describe the proposed partnership, and 2) a Multiscale Modeling (MSM) Consortium Plan. All awardees from this cooperative agreement FOA will be required to participate in the Interagency Modeling and Analysis Group (IMAG) MSM Consortium to contribute to the greater multiscale modeling community, http://www.imagwiki.org/mediawiki.

The Predictive Multiscale Models for Biomedical, Biological, Behavioral, Environmental and Clinical Research Program Announcement uses the U01 cooperative agreement mechanism. Project requirements (described below), milestones and timeline for both scientific progress and participation within the MSM Consortium will be reviewed (Section V) and established prior to funding, and must be met prior to funding of each subsequent budget period. Investigators funded from this FOA are expected to play an active role in the MSM Consortium, leading the working groups, sharing data, models, expertise and other efforts to contribute to the greater multiscale modeling community. Applicants to this FOA must allocate funds for at least two key investigators with complementary expertise to travel to the annual MSM Consortium Meetings (http://www.imagwiki.org/mediawiki/index.php?title=IMAG/MSM_Events). Program staff from the IMAG award agency will have a significant, although not dominant, role in the planning and execution of the supported activities. In addition, IMAG program staff will promote the mission of the MSM Consortium, organize annual meetings, facilitate awardee participation in the Consortium activities, and have a significant role in the assessment of annual milestone performance.

Investigators are required to identify a compelling multiscale problem or approach that is currently not being addressed - that is, beyond current practice - and address its impact on the field. The proposed multiscale model must incorporate substantial representations of the underlying biological or behavioral mechanisms from at least two scales and at least one linkage between scales. These multiscale models may also include dynamical processes which span multiple time and spatial scales.

Investigators are required to provide rationale for the predictive aspects of the proposed multiscale model. Furthermore, investigators are required to provide a convincing technical plan for achieving predictive outcomes from the model. Predictive models generate new hypotheses, and do not merely recapitulate the data that were used to build them. Challenges to predictive multiscale modeling arise as a result of our limited understanding of the complex, dynamic nature of the biological or behavioral system, the availability of and limited access to good quality data, and the difficulties involved in understanding, communicating, and sharing modeling methods among multiple disciplines. It may be beneficial to use both bottom-up and top-down approaches to multiscale modeling to facilitate the development of predictive models.

The data used to develop the model must be identified and appropriately justified for each scale and link modeled. Parameter estimation and model validation should be based on experimental and/or observational data as appropriate. The use and development of standard datasets are strongly encouraged. As a part of the IMAG/MSM Consortium (http://www.imagwiki.org/mediawiki) funded investigators of this FOA will interact with this community of modelers to further promote DATA sharing and scientific collaboration.

Investigators must clearly describe the model architecture and highlight aspects of the architecture which will facilitate model sharing. Models must be designed so that components or modules within the models are clearly documented and can be independently and explicitly shared with other modelers. Investigators are strongly encouraged to propose plans to link proposed models with other relevant models. As a part of the IMAG/MSM Consortium (http://www.imagwiki.org/mediawiki) funded investigators of this FOA will interact with this community of modelers to further promote MODEL sharing and scientific collaboration.

Investigators are expected to include appropriate data, model and software sharing plans to collaborate with others not on the investigative team and allow others external to the investigative team to test, validate, reuse and extend the models (see section IV.2 Plan for Sharing Models and Software). Investigators are strongly encouraged to employ standardized ontologies and languages for model representation where appropriate (e.g. domain-specific Extensible Markup Language (XML)-based model representations such as SBML and CellML). Current discussions on data and modeling sharing can be found on the IMAG wiki (http://www.imagwiki.org/mediawiki/index.php?title=Multiscale_Modeling_Working_Groups). Investigators are encouraged to budget for and plan model repositories, and appropriate software engineering efforts. The benefits of software engineering practices are expected to include, but are not limited to, improved functionality by linking disparate but scientifically appropriate software, reduction of redundant software efforts, efficient software reuse, and improvement in quality of software by opening the development process to more scientists.

Investigators are welcome to use advanced computational resources to support fundamental research and technology development to achieve a predictive, systems-level understanding of complex biological systems. Advanced computing research could provide model development capabilities, data analytics, frameworks for integration and collaboration, and uncertainty quantification and as such computing frameworks are needed whereby multi-disciplinary, multi-scale data can be integrated with process models to examine coupled phenomena across a range of scales. Ideally, these frameworks would be flexible enough to enable community-level modeling efforts that integrate data and modeling approaches across a wide spectrum of biological, behavioral, clinical and environmental science disciplines. An ability to connect data with models from a wide variety of sources enables more holistic and robust predictions of complex system behavior. The DOE's Office of Science supports a computing user facility, National Energy Research Scientific Computing Center (http://www.nersc.gov/) that will enhance computational research in biology. As well, the NSF Office of Cyberinfrastructure supports the TeraGrid facility (www.teragridforum.org), an open scientific discovery infrastructure combining leadership class resources at nine partner sites to create an integrated, persistent computational resource, which will also enhance computational research in biology.

Investigators interested in 1) proposing to develop models at a single biological or behavioral scale, or at multiple scales without crossing between scales; 2) proposing multiscale modeling without an explicit predictive component; 3) proposing multiscale modeling without representative biological or behavioral mechanisms; 4) proposing to develop models that do not incorporate a model architecture that will facilitate model sharing; or 5) proposing a project that does not include a Partnership Plan or a MSM Consortium Plan should respond to other FOAs.

Specific interests:

The following section briefly describes the specific interests of the participating funding components of this FOA. All interests are examples and are not limited to these cases.

The National Institute of Biomedical Imaging and Bioengineering (NIBIB) is interested in supporting the development of predictive multiscale models that have broad therapeutic and interventional applications in diseases or health conditions. Other areas of interest include multiscale modeling to complement technology development in all other program areas of the NIBIB, http://www.nibib.nih.gov/Research/ProgramAreas.

The National Cancer Institute (NCI) is interested in supporting the development of predictive multiscale models of cancer processes. These models may be designed to elucidate basic mechanisms underlying cancer initiation and progression and/or to address important translational, clinical or epidemiological questions related to cancer risk, prevention, diagnosis and treatment.

The National Center for Research Resources (NCRR) supports research to design, create, develop, and disseminate innovative technologies and techniques with broad applicability to biomedical research. In MSM this may include but is not limited to creation of reusable models that integrate data and knowledge across fields, scales, and modalities and enable synergistic combining of technologies to develop new ways to look at complex problems; novel methods to fuse data from different conceptual frameworks with diverse levels of accuracy, granularity, and reliability; techniques that combine logical and probabilistic models to enable processing of incomplete and/or conflicting data; models that incorporate uncertainty quantification; models that enable identification of knowledge gaps.

The National Human Genomic Research Institute (NHGRI) is interested in the development of multiscale models to predict genetic/genomic effects and gene-environment interactions on phenotypes in model organisms or on the physiology, pathology, pharmacology, clinical phenotype progression/regression, and medication selections for disease treatment to use genomics to advance the science of medicine.

The National Heart, Lung, and Blood Institute (NHLBI) is interested in supporting innovative modeling methods and experimental approaches to facilitate predictive multiscale models of the physiology and pathophysiology of the cardiovascular, pulmonary, hematological and sleep systems.

The National Institute on Aging (NIA) is interested in supporting research on multiscale models that link molecular mechanisms with age-related changes in cognition, emotion, vision, taste, smell, touch, audition, motor, endocrine, metabolic, cardiovascular, hematopoietic, renal, immunologic, and musculoskeletal function; on age-related changes in inflammation and adaptation to stress; on predictive models of age-related increases in organ fibrosis or adipose cell infiltration; and on predictive models of Alzheimer's disease, frontotemporal dementia, and delirium.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is interested in supporting multiscale modeling research related to the causes, consequences, treatment, and prevention of alcohol-related problems and alcohol use disorders. Examples of research topics include but are not limited to: models that characterize interactions between individual-level alcohol-related behaviors and population-level health and economic outcomes; models to explore underlying mechanisms of individual-, community-, or population-level preventive interventions; and models of the determinants and mechanisms underlying changes in drinking before, during, and after treatment, as well as treatment-seeking and utilization.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is interested in predictive multiscale modeling related to a diverse set of research interests, including physiological and pathophysiological function related to the health, productivity, independence, and quality-of-life of people with disabilities, normal and/or abnormal development over time, and health and dynamics of human populations.

The National Institute on Drug Abuse (NIDA) is interested in supporting multiscale modeling research that links molecular mechanisms, intracellular signaling networks, or neural plasticity at the single cell level with brain function or behavior of relevance to understanding drug abuse and addiction. Also of interest are multiscale models that can aid in the prediction of physiological systems pathologies from drug effects at the cellular level and multiscale models that include social networks or populations. Finally, NIDA is interested in treatment and prevention services multiscale modeling to support decision making within and among systems of care which can span organizational, temporal, and geospatial scales.

The National Institute of Environmental Health Sciences (NIEHS) is interested in the development of multiscale models that link personal exposure to mechanistic and phenotypic endpoints and that enable prediction of the biological effects of exposure. An emphasis is placed on efforts that reflect "real world' exposures such as complex chemical mixtures; the interaction between chemical exposures with genetic susceptibility or lifestyle factors; or chronic, low dose exposures.

The National Institute of General Medical Sciences (NIGMS) is interested in supporting research in multiscale modeling methods that apply to the core areas of (http://www.nigms.nih.gov/Research/) of cell biology, biophysics, genetics, developmental biology, pharmacology, physiology, biological chemistry. NIGMS is also interested in new or innovative multiscale methods in computational science related to biomedical research. In addition, NIH has a new program in computational social sciences/social, population, and behavioral modeling research. One major objective of this program is to connect systems biologists with researchers using systems approaches at that link physiology to population.

The Department of Energy (DOE) Office of Biological and Environmental Research (BER) advances world-class biological and environmental research programs and scientific user facilities to support DOE's energy, environment, and basic research missions. The Biological Systems Science Division (BSSD, http://www.sc.doe.gov/ober/bssd_top.html) provides the scientific and analytical technologies needed to translate genomic sequence into a profound and comprehensive understanding of the myriad of processes carried out by biological systems. Research within this program leverage the genomic code as a starting point to understand systems biology through (1) Systems analysis of the collective -omics (e.g. transcriptomics, proteomics and metabolomics) of plants and microbes, (2) Development of new methods for characterizing and imaging molecular systems, and (3) Development of new approaches to synthesize and redesign biology processes. Applicants interested in DOE funding may wish to use the September due dates.

The Food and Drug Administration (FDA) is interested in development of predictive multiscale models of the anatomy, physiology and pathophysiology of the cardiovascular, pulmonary, orthopedic, ophthalmic, and neurological systems. Research that advances our understanding of the performance of medical products in humans are of greatest interest. To facilitate more effective medical product development, improved engineering analysis methods are needed to predict whether a proposed design will function properly and safely based on the intended function of the product and the anatomic and physiologic data gathered. Computational modeling should be integrated with in vitro and in vivo experiments in such a way that these distinct elements and their interplay will cumulatively guide product development and provide a more informative evaluation pathway.

The National Science Foundation (NSF) is the only federal agency dedicated to the support of basic research and education across all fields of science and engineering, in fulfillment of its statutory mission "to promote the progress of science; to advance the national health, prosperity, and welfare; and to secure the national defense." Participating NSF components are interested in supporting research at the interfaces of the life sciences, computational sciences, mathematical and physical sciences, and engineering to accelerate understanding of biological and biomedical systems. Advances in methods and tools for predictive modeling, simulation, and analysis of emergent behavior in complex multiscale systems are of interest, including the issues of verification, validation, and uncertainty quantification across scales. Advances in data-analysis techniques and tools that are relevant to these systems are also of interest, in particular for impact on the "data deluge."

Applicants focusing on specific disease or domain not aligned with the mission of the NIH components and participating agencies on these FOAs should contact the NIH Institute or Center or agency to find FOAs that are more appropriate to their research interest.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

All applications must include an MSM Consortium Plan as described in Section IV. Content and Form of Application Submission. Applications lacking the MSM Consortium Plan will not be peer reviewed.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-203.html.

BASIC RESEARCH IN CALCIFIC AORTIC VALVE DISEASE (R01): RFA-HL-12-015

Components of Participating Organizations

National Heart, Lung, and Blood Institute

Application Receipt Date(s): October 11, 2011

The purpose of this FOA is to encourage innovative molecular and physiological research that could lead to early diagnosis or effective medical therapy for calcific aortic valve disease. Applications from investigators in related fields (for example, mineralization and bone physiology, extracellular matrix physiology, and molecular imaging) are strongly encouraged.

Applicants must describe in the application how the proposed research could lead to early diagnosis or effective medical therapy for calcific aortic valve disease.

Calcific aortic valve disease (CAVD) covers a spectrum of disease from initial changes in the cell biology of the valve leaflets, through early calcification, tissue remodeling and aortic sclerosis, to outflow obstruction and aortic stenosis. Although similar to vascular atherosclerosis, CAVD is a distinct, actively regulated disease process that can't be characterized simply as "senile"• or "degenerative"•

CAVD is more common with age, but it's not an inevitable consequence of aging. The overall prevalence of aortic stenosis in the US is 0.4%, but the figure increases to 1.3% for those over 65 years old and to 2.8% for those over 75 years old. Epidemiological studies show that some of the risk factors for CAVD are similar to those for vascular atherosclerosis. In addition to age, gender and certain clinical factors are associated with an increased risk of CAVD. However, the factors associated with initiation of CAVD may differ from those associated with progression of the disease.

Surgical replacement of the aortic valve remains the definitive treatment and is second only to CABG among major cardiothoracic surgical procedures. Over 30,000 aortic valves were replaced in 2009.

There is no effective medical therapy for CAVD. Two recent major clinical trials failed to demonstrate benefit from statin therapy despite reduction in lipid levels. These results highlight the distinction between CAVD and vascular atherosclerosis. One possible explanation is that statin therapy was initiated too late in the course of CAVD to be effective. This explanation highlights the need for diagnostic techniques that can detect initial events in the disease process.

CAVD is not atherosclerosis. Despite similarities, tissue calcification in CAVD is more severe, and the clinical consequences result from stiffness of the valve leaflets rather than plaque formation and rupture. The severity of CAVD and coronary or vascular atherosclerosis in an individual patient is often discordant.

Additional background information is available in the report of the NHLBI Working Group on Calcific Aortic Stenosis and in Otto CM, N Engl J Med 2008;359(13):1395-8.

The purpose of this FOA is to encourage innovative molecular and physiological research that could lead to early diagnosis or effective medical therapy for calcific aortic valve disease, for example through new diagnostic biomarkers or new therapeutic targets. Appropriate research topics include but are not limited to those listed below:

  • Cell biology: signaling pathways, the role of valve interstitial and endothelial cells.

  • Extracellular matrix: composition, mechanical properties, communication with cells.

  • Biomechanics: micro-scale transduction, macro-scale hemodynamics.

  • Physiology: mechanisms and regulation of calcification, bone mineralization, comparison with vascular calcification.

  • Comorbidities: diabetes, metabolic syndrome, and chronic kidney disease.

  • Diagnosis: molecular imaging, biomarkers for early events in initiation and progression.

  • Genetics: genetics of CAVD and bicuspid aortic valve.

  • Infrastructure: improved animal models, access to human valve tissue.

This announcement focuses on CAVD. Research on vascular atherosclerosis, coronary atherosclerosis, or calcification in other contexts (including but not limited to coronary, vascular, aortic, or annular) is not responsive to this announcement, unless preliminary data link the research to CAVD. Purely clinical research, clinical trials, or epidemiological research is not responsive to this announcement.

Grantees may be asked to provide information to evaluate the success of this research program. The program may be evaluated by the number of related publications, the number of potential diagnostic techniques or therapeutic targets identified for further research, and expansion of the network of investigators in CAVD.

Investigators should plan to attend a grantee meeting in the Bethesda MD area during the final year of the program and budget accordingly.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization. All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-015.html.

PULMONARY VASCULAR-RIGHT VENTRICULAR AXIS RESEARCH PROGRAM (R01): RFA-HL-12-021

Components of Participating Organizations

National Heart, Lung, and Blood Institute

Application Receipt Date(s): October 13, 2011

The purpose of this FOA is to support a novel multidisciplinary and coordinated research effort to acquire critical disease-defining knowledge of the pulmonary vascular-RV axis in human subjects leading to improved and targeted diagnostics and therapeutics for right ventricular failure (RVF). The pulmonary circulation is intimately coupled with RV function in health and disease and it is clear that patients with lung vascular disease, particularly pulmonary arterial hypertension (PAH), die because of RVF. It is unclear whether RVF and disease occurs only secondary to afterloading effects, or whether the diseased lung vasculature is essential to cause loss of RV compensatory mechanisms during loading. Furthermore, our understanding of clinical RVF is limited because: 1) current concepts of RVF mechanisms have been shaped largely by inference from investigations of left ventricular failure, despite evidence that the RV and LV may differ in their respective responses to increasing afterload; 2) no detailed knowledge base exists in humans, including genetic/genomic data, regarding the transition from compensatory RV hypertrophy to RVF; and 3) a coordinated effort between pulmonary vascular researchers and cardiac failure investigators has not been specifically fostered to acquire this knowledge. Therefore, this research program will support meritorious human subjects research (NIH definition) acquiring knowledge of human RVF through studies involving the pulmonary vascular-right ventricular axis. For each individual R01 project, a multidisciplinary approach will be required. Multidisciplinary "teams" should be constituted by experts in cardiovascular biology, heart failure, and/or clinical cardiology, with expertise in lung vascular biology and disease and/or pulmonology. In addition to the core expertise in cardiac and lung vascular research, expertise may also include imaging, bioengineering, epidemiology, genetics, or any other discipline necessary to produce a robust research project. Proposals should be hypothesis-driven.

Specific Areas of Research Interest: Examples of studies could include, but are not limited to: defining factors regulating pulmonary circulation-RV dynamics and developing novel measures to assess function/dysfunction; elucidating factors controlling RV growth, injury and repair in conjunction with lung vascular disease development; elucidating biomarkers or other signs indicative of RV reprogramming in the setting of lung vascular disease; discriminating afterload effects from lung vasculopathic-dependent processes of RV dysfunction, compensation, and failure; conducting genetic and epigenetic studies of the lung vascular-right ventricular axis in health and disease; conducting genomic and/or proteomic studies leveraging existing cohorts and/or populations in which RV function can be followed; and testing pilot interventions in well-described lung vascular disease patients in which novel or validated RV indices can be measured and followed.

Furthermore, projects proposing to develop new reagents for use in human subjects studies of the pulmonary vascular-right ventricular axis, apply novel imaging approaches or modalities, develop model systems using human subjects research-derived data, or invent tools for advancing mechanistic research into human lung vascular disease and RVF, will also be considered responsive to this Program. Studies which interrogate RV compensatory mechanisms in the setting of adult congenital heart disease and/or pulmonary thromboembolic disease are also encouraged.

Human subjects research (http://grants.nih.gov/grants/policy/hs/) must be proposed. Projects proposing only animal model studies will not be reviewed.

Principal Investigators who are awarded support under this program will be expected to meet on an annual basis to discuss emerging findings from their respective projects.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

It is expected that key personnel will be constituted by multidisciplinary expertise. Core expertise involving investigators with cardiac and lung vascular expertise is required. A multiple PD/PI plan is strongly encouraged.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-021.html.

PATHOPHYSIOLOGY OF HIV-ASSOCIATED NEURODEGENERATION IN AGING POPULATIONS ON LONG-TERM ANTI-RETROVIRAL THERAPY (R01): RFA-MH-12-070

Components of Participating Organizations

National Institute of Mental Health

National Institute on Aging

National Institute of Neurological Disorders and Stroke

Application Receipt Date(s): September 09, 2011

The National Institute of Mental Health (NIMH), the National Institute on Aging (NIA), and the National Institute of Neurological Disorders and Stroke (NINDS) invite research grant applications focused on elucidating the mechanisms of HIV-associated neuropathogenesis in the context of aging, chronic infection with HIV, and long term exposure to Highly Active Antiretroviral Therapy (HAART). The neuropathogenic mechanisms of HIV-Associated Neurocognitive Disorders (HAND) may be distinct in the aging HIV-infected populations given the potential interactions between aging associated events, HIV-associated neurodegenerative processes, and exposure to HAART. Understanding the pathogenesis of HAND in HIV-infected individuals over 50 years of age, in light of potential interactions with HAART, neurodegenerative diseases, and aging-related co-morbid conditions are the focus of this announcement. Applications ranging from basic research to clinical diagnosis and treatment in domestic and international settings are of interest. Multidisciplinary research teams and collaborative alliances are encouraged, but not required.

A major age-related demographic shift in HIV-infected patients has been noted by clinicians and documented by the Center for Disease Control (CDC). The CDC projects that by 2015, more than half of all HIV-infected individuals in the United States will be over the age of 50. During the next decade, a rapid increase in HIV prevalence among the elderly is expected to derive from two subpopulations: (1) HIV-diagnosed cases of a "younger group"• surviving into older age because of the efficacy of HAART in reducing mortality; and (2) newly HIV-infected cases of an "older group". Coupled with the aging process, the extended exposure of these adults to both HIV and antiretroviral drugs appears to increase their risk of illness and death from cardiovascular, bone, kidney, liver, lung, neurologic and neuropsychiatric complications. While all of these complications impact HIV-infected aging populations the focus of this announcement is to stimulate research on the pathophysiology and treatment of HAND in HIV-infected people over 50 years of age who are on HAART.

The prevalence of HAND remains high despite wide spread use of anti-retroviral therapy. A recently completed large epidemiologic study by the CHARTER (CNS HIV Anti-retroviral Effects Research) group examined 1,574 participants cross-sectionally and 657 participants longitudinally and has reported a HAND prevalence rate of greater than 50% in HIV infected individuals in the United States. Recent studies are showing that the phenotype of neurologic and neurocognitive complications are evolving in the era of HAART. In an effort to accurately classify the phenotypic changes seen in the HAART era, a revised American Academy of Neurology definitional criteria for HAND was adopted. The categories of HAND include Asymptomatic Neurocognitive Impairment (ANI), Mild Neurocognitive Disorder (MND), and HIV-Associated Dementia (HAD). In the current treatment environment, MND is the most prevalent form of HAND; yet even mild neurocognitive deficits can interfere with activities of daily living and reduce the quality of life in long-standing aviremic HIV-positive patients.

The pathophysiology of HAND may be distinct in older HIV-infected patients given the potential interactions between HIV-associated neurodegenerative processes, long term HAART, and aging-associated events. HIV-involvement of the brain has traditionally been classified as a subcortical dementia with productive infection of perivascular macrophages, microglia, and restrictive infection of astrocytes, but not neurons. Recent research suggests that both cortical and subcortical areas of the brain are affected by HIV in the HAART era. Additionally, functional MRI scans, which link neural activity levels to measured changes in cerebral blood flow and oxygenation in the brain, found HIV-positive subjects to be functionally equivalent to HIV-negative patients who were 15-20 years older. Long term HAART has been associated with increased neuronal toxicity and has been shown to exacerbate cerebrovascular disease resulting from hypercholesterolemia and diabetes. Coincident with the introduction of HAART, the rate of hospitalization due to ischemic stroke in HIV-infected patients rose by 67% between 1997 and 2006. As HIV-infected patients are growing older, adverse effects of HAART and drug-drug interactions with aging-related diseases and medications become relatively more important. Given the potential for synergy between HIV and aging, further research to determine whether HIV-related injury to the brain continues to accrue in some patients is needed.

There is a growing body of research indicating overlapping neuropathologic features between aging-associated neurodegenerative disease and HAND. Although the brain pathology differs between HAND and Alzheimer's disease, HIV-positive brains derived from patients over 50 years of age have been shown to accumulate abnormal proteins including amyloid, alpha-synuclein, and hyper-phosphorylated tau. Measurements of ß-Amyloid (1-42) in the CSF of cognitively impaired patients with HIV were noted to be similar to those in patients with mild dementia of the Alzheimer type. The mechanism of HIV induced dysregulation of amyloid expression is an area of considerable research. For example, HIV Tat protein has been shown to inhibit neprilysin; a neuronal amyloid-beta degrading enzyme. Other studies have examined the impact of HIV on control of amyloid-beta production, solubility and clearance. Additional research to further define mechanisms of HIV-induced dysregulation of protein clearance and impact on neurodegenerative processes is needed.

The role of host genetic factors in determining susceptibility of the aging to HAND is also of interest for this initiative. Epidemiological data from the Hawaii Aging with HIV cohort demonstrated an association between the genetic apolipoprotein-epsilon4 allele, APOE-E4, and dementia among older, but not among younger HIV-1-infected patients. Other investigators have examined the relationship between cerebrospinal fluid apolipoprotein E (APOE) levels, the expression of various APOE alleles and cognitive impairment. Their research suggests that the relatively higher levels of CSF APOE in E4+ HIV+ (having APOE-E4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the E4 allele (with APOE-E2 and APOE-E3 isoforms) may show compensatory responses that lead to better cognitive performance. These initial studies have yielded valuable data and further research is needed to identify other host genetic factors that may predict the CNS metabolic, vascular, and neurobiological events that impact neurocognitive outcomes in aging HIV-infected individuals.

A variety of immunologic factors may also contribute to neurodegenerative processes in aging HIV-infected individuals. For example, the continued prevalence of cognitive impairment despite good virologic control in the era of HAART may be due to a "legacy effect"• resulting from a history of advanced immunosuppression accompanied by high plasma viral load and low CD4 nadir. Age-associated declines in immune function, termed immunosenescence, may also impact HAND in the over 50 HIV-positive population. Senescence of T cells is normal given that production of naïve T lymphocytes by the thymus is reduced after the age of 50. Aging and chronic HIV-infection are both associated with activation of the immune system, increased levels of circulating inflammatory mediators, and inflammation which may have a significant impact on HIV-associated CNS disease.

In summary, the goal of this announcement is to define and elucidate novel mechanisms of pathogenesis that are driving neurocognitive decline at the intersection of HIV-associated neurodegenerative processes, aging associated CNS disease, chronic HAART treatment effects, and host susceptibility factors. The ultimate goal of this initiative is to help develop novel strategies for treatment of neurocognitive impairment in the HIV positive aging population.

The research areas that are pertinent to this FOA include, but are not limited to, the items listed below:

  • Appraise the pathogenic mechanisms and cell & molecular basis of HIV-associated neurocognitive dysfunction in the over 50 HIV-infected population;

  • Investigate aspects of HIV infection that uniquely influence the aging nervous system and impact on the neurocognitive dysfunction in the over 50 HIV-infected population;

  • Assess the mechanism of HIV, the effects of HAART, and aging related co-morbid conditions (diabetes, hypercholesterolemia, stroke) on cerebrovascular factors that cause neurocognitive impairment;

  • Ascertain the potential for drug-drug interactions between HAART and aging-related drugs including antidepressants, antiepileptics, and analgetics;

  • Determine the means to differentiate between adverse effects of HAART on the CNS verses general aging and symptoms of HIV itself;

  • Examine common pathways and compare the effects of aging processes in the brain (e.g., atrophy, neurotransmitter changes, alterations in BBB integrity), age-related neurodegenerative disease (e.g., Alzheimer's disease, vascular dementia), and HAND in older adults;

  • Elucidate the pathways leading to dysregulated expression of amyloid-beta, amyloid precursor protein, tau and synuclein as a result of chronic HIV infection/inflammation and long term HAART;

  • Assess the impact of HIV on autophagy and clearance of misfolded proteins in neurodegenerative processes;

  • Examine the effects of mitochondrial dysfunction associated with HIV and aging;

  • Determine the impact of dysregulation of axonal transport in HIV-associated aging processes;

  • Ascertain the role of neurotrophic factors in the repair mechanisms in HIV-related aging events;

  • Assess the mechanisms of synaptodendritic degeneration associated with HIV and aging;

  • Develop novel animal models to study the effects of HIV and aging-related factors in neurodegenerative disease processes;

  • Examine the contribution of CNS inflammation and persistent immunodeficiency resulting from aging associated immunosenescence to the pathogenesis of HIV-induced neurocognitive dysfunction in the over 50 HIV-infected population;

  • Define host genetic factors that alter susceptibility to accelerated HIV-associated aging events and impact neurocognitive outcomes;

  • Utilize imaging approaches to understand HIV-related neurodegeneration in relation to age-related neurodegenerative diseases;

  • Identify and validate biomarkers that provide insight into the pathogenesis of HAND in the aging HIV-infected population, or aid in distinguishing HAND from other aging-related neurocognitive disorders (For example; neopterin, Abeta42, APOE4, tau, phospho-tau, and metabolic biomarkers associated with impaired blood flow to the brain);

  • Characterize the CNS manifestation of HIV-associated immune reconstitution inflammatory syndromes in aging, HIV-infected adults.

The use of resources from large NIH-funded HIV related studies such as Multi-Center AIDS Cohort Study (MACS), Women's Interagency HIV Study (WIHS), CNS HIV Antiretroviral Therapy Effects Research (CHARTER), the National NeuroAIDS Tissue Consortium (NNTC) and the HIV Brain Sequence Database is encouraged.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-MH-12-070.html.

PATHOPHYSIOLOGY OF HIV-ASSOCIATED NEURODEGENERATION IN AGING POPULATIONS ON LONG-TERM ANTI-RETROVIRAL THERAPY (R21): RFA-MH-12-071

Components of Participating Organizations

National Institute of Mental Health

National Institute on Aging

National Institute of Neurological Disorders and Stroke

Application Receipt Date(s): September 09, 2011

The National Institute of Mental Health (NIMH), the National Institute on Aging (NIA), and the National Institute of Neurological Disorders and Stroke (NINDS) invite research grant applications focused on elucidating the mechanisms of HIV-associated neuropathogenesis in the context of aging, chronic infection with HIV, and long term exposure to Highly Active Antiretroviral Therapy (HAART). The neuropathogenic mechanisms of HIV-Associated Neurocognitive Disorders (HAND) may be distinct in the aging HIV-infected populations given the potential interactions between aging associated events, HIV-associated neurodegenerative processes, and exposure to HAART. Understanding the pathogenesis of HAND in HIV-infected individuals over 50 years of age, in light of potential interactions with HAART, neurodegenerative diseases, and aging-related co-morbid conditions are the focus of this announcement. Applications ranging from basic research to clinical diagnosis and treatment in domestic and international settings are of interest. Multidisciplinary research teams and collaborative alliances are encouraged, but not required.

A major age-related demographic shift in HIV-infected patients has been noted by clinicians and documented by the Center for Disease Control (CDC). The CDC projects that by 2015, more than half of all HIV-infected individuals in the United States will be over the age of 50. During the next decade, a rapid increase in HIV prevalence among the elderly is expected to derive from two subpopulations: (1) HIV-diagnosed cases of a "younger group"• surviving into older age because of the efficacy of HAART in reducing mortality; and (2) newly HIV-infected cases of an "older group". Coupled with the aging process, the extended exposure of these adults to both HIV and antiretroviral drugs appears to increase their risk of illness and death from cardiovascular, bone, kidney, liver, lungs, neurologic and neuropsychiatric complications. While all of these complications impact HIV-infected aging populations the focus of this announcement is to stimulate research on the pathophysiology and treatment of HIV-Associated Neurocognitive Disorders (HAND) in HIV-infected people over 50 years of age who are on HAART.

The prevalence of HAND remains high despite wide spread use of anti-retroviral therapy. A recently completed large epidemiologic study by the CHARTER (CNS HIV Anti-retroviral Effects Research) group examined 1,574 participants cross-sectionally and 657 participants longitudinally and has reported a HAND prevalence rate of greater than 50% in HIV infected individuals in the United States. Recent studies are showing that the phenotype of neurologic and neurocognitive complications are evolving in the era of highly active antiretroviral therapy (HAART). In an effort to accurately classify the phenotypic changes seen in the HAART era, a revised American Academy of Neurology definitional criteria for HAND was adopted. The categories of HAND include Asymptomatic Neurocognitive Impairment (ANI), Mild Neurocognitive Disorder (MND), and HIV-Associated Dementia (HAD). In the current treatment environment, MND is the most prevalent form of HAND; yet even mild neurocognitive deficits can interfere with activities of daily living and reduce the quality of life in long-standing aviremic HIV-positive patients.

The pathophysiology of HAND may be distinct in older HIV-infected patients given the potential interactions between HIV-associated neurodegenerative processes, long term HAART, and aging-associated events. The effect of HIV on the brain has traditionally been classified as a subcortical dementia with productive infection of perivascular macrophages, microglia, and restrictive infection of astrocytes, but not neurons. Recent research suggests that both cortical and subcortical areas of the brain are affected by HIV in the HAART era. Additionally, functional MRI scans, which link neural activity levels to measured changes in cerebral blood flow and oxygenation in the brain, found HIV-positive subjects to be functionally equivalent to HIV-negative patients who were 15- 20 years older. Long term HAART has been associated with increased neuronal toxicity and has been shown to exacerbate cerebrovascular disease resulting from hypercholesterolemia and diabetes. Coincident with the introduction of HAART, the rate of hospitalization due to ischemic stroke in HIV-infected patients rose by 67% between 1997 and 2006. As HIV-infected patients are growing older, adverse effects of HAART and drug-drug interactions with aging-related diseases and medications become relatively more important. Given the potential for synergy between HIV and aging, further research to determine whether HIV-related injury to the brain continues to accrue in some patients is needed.

There is a growing body of research indicating overlapping neuropathologic features between aging-associated neurodegenerative disease and HAND. Although the brain pathology differs between HAND and Alzheimer's disease, HIV-positive brains derived from patients over 50 years of age have been shown to accumulate abnormal proteins including amyloid, alpha-synuclein, and hyper-phosphorylated tau. Measurements of β-Amyloid (1-42) in the CSF of cognitively impaired patients with HIV were noted to be similar to those in patients with mild dementia of the Alzheimer type. The mechanism of HIV induced dysregulation of amyloid expression is an area of considerable research. For example, HIV Tat protein has been shown to inhibit neprilysin; a neuronal amyloid-beta degrading enzyme. Other studies have examined the impact of HIV on control of amyloid-beta production, solubility and clearance. Additional research to further define mechanisms of HIV-induced dysregulation of protein clearance and impact on neurodegenerative processes is needed.

The role of host genetic factors in determining susceptibility of the aging to HAND is also of interest for this initiative. Epidemiological data from the Hawaii Aging with HIV cohort demonstrated an association between the genetic apolipoprotein-epsilon4 allele, APOE-E4, and dementia among older, but not among younger HIV-1-infected patients. Other investigators have examined the relationship between cerebrospinal fluid apolipoprotein E (APOE) levels, the expression of various APOE alleles and cognitive impairment. Their research suggests that the relatively higher levels of CSF APOE in E4+ HIV+ (having APOE-E4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the E4 allele (with APOE-E2 and APOE-E3 isoforms) may show compensatory responses that lead to better cognitive performance. These initial studies have yielded valuable data and further research is needed to identify other host genetic factors that may predict the CNS metabolic, vascular, and neurobiological events that impact neurocognitive outcomes in aging HIV-infected individuals.

A variety of immunologic factors may also contribute to neurodegenerative processes in aging HIV-infected individuals. For example, the continued prevalence of cognitive impairment despite good virologic control in the era of HAART may be due to a "legacy effect"• resulting from a history of advanced immunosuppression accompanied by high plasma viral load and low CD4 nadir. Age-associated declines in immune function, termed immunosenescence, may also impact HAND in the over 50 HIV-positive population. Senescence of T cells is normal given that production of naïve T lymphocytes by the thymus is reduced after the age of 50. Aging and chronic HIV-infection are both associated with activation of the immune system, increased levels of circulating inflammatory mediators, and inflammation which may have a significant impact on HIV-associated CNS disease.

In summary, the goal of this announcement is to define and elucidate novel mechanisms of pathogenesis that are driving neurocognitive decline at the intersection of HIV-associated neurodegenerative processes, aging associated CNS disease, chronic HAART treatment effects, and host susceptibility factors. The ultimate goal of this initiative is to help develop novel strategies for treatment of neurocognitive impairment in the HIV positive aging population.

The research areas that are pertinent to this FOA include, but are not limited to, the items listed below:

  • Appraise the pathogenic mechanisms and cell & molecular basis of HIV-associated neurocognitive dysfunction in the over 50 HIV-infected population;

  • Investigate aspects of HIV infection that uniquely influence the aging nervous system and impact on the neurocognitive dysfunction in the over 50 HIV-infected population;

  • Assess the mechanism of HIV, the effects of HAART, and aging related co-morbid conditions (diabetes, hypercholesterolemia, stroke) on cerebrovascular factors that cause neurocognitive impairment;

  • Ascertain the potential for drug-drug interactions between HAART and aging-related drugs including antidepressants, antiepileptics, and analgetics;

  • Determine the means to differentiate between adverse effects of HAART on the CNS verses general aging and symptoms of HIV itself;

  • Examine common pathways and compare the effects of aging processes in the brain (e.g., atrophy, neurotransmitter changes, alterations in BBB integrity), age-related neurodegenerative disease (e.g., Alzheimer's disease, vascular dementia), and HAND in older adults;

  • Elucidate the pathways leading to dysregulated expression of amyloid-beta, amyloid precursor protein, tau and synuclein as a result of chronic HIV infection/inflammation and long term HAART;

  • Assess the impact of HIV on autophagy and clearance of misfolded proteins in neurodegenerative processes;

  • Examine the effects of mitochondrial dysfunction in associated with HIV and aging;

  • Determine the impact of dysregulation of axonal transport in HIV-associated aging processes;

  • Ascertain the role of neurotrophic factors in the repair mechanisms in HIV-related aging events;

  • Assess the mechanisms of synaptodendritic degeneration associated with HIV and aging;

  • Develop novel animal models to study the effects of HIV and aging-related factors in neurodegenerative disease processes;

  • Examine the contribution of CNS inflammation and persistent immunodeficiency resulting from aging associated immunosenescence to the pathogenesis of HIV-induced neurocognitive dysfunction in the over 50 HIV-infected population;

  • Define host genetic factors that alter susceptibility to accelerated HIV-associated aging events that impact on neurocognitive outcomes;

  • Utilize imaging approaches to understand HIV-related neurodegeneration in relation to age-related neurodegenerative diseases;

  • Identify and validate biomarkers that provide insight into the pathogenesis of HAND in the aging HIV-infected population, or aid in distinguishing HAND from other aging-related neurocognitive disorders (For example; neopterin, Abeta42, APOE4, tau, phospho-tau, and metabolic biomarkers associated with impaired blood flow to the brain);

  • Characterize the CNS manifestation of HIV-associated immune reconstitution inflammatory syndromes in aging, HIV-infected adults.

The use of resources from large NIH-funded HIV related studies such as Multi-Center AIDS Cohort Study (MACS), Women's Interagency HIV Study (WIHS), CNS HIV Antiretroviral Therapy Effects Research (CHARTER), the National NeuroAIDS Tissue Consortium (NNTC) and the HIV Brain Sequence Database is encouraged.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-MH-12-071.html.

MENTORED RESEARCH SCIENTIST DEVELOPMENT AWARD (PARENT K01): PA-11-190

Components of Participating Organizations

National Institutes of Health

National Center for Complementary and Alternative Medicine

National Center for Research Resources

National Human Genome Research Institute

National Heart, Lung, and Blood Institute

National Institute on Aging

National Institute on Alcohol Abuse and Alcoholism

National Institute of Allergy and Infectious Diseases

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Institute of Biomedical Imaging and Bioengineering

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Drug Abuse

National Institute on Deafness and Other Communication Disorders

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

National Institute of Nursing Research

Office of Dietary Supplements

Application Receipt/Submission Date(s): Multiple dates, see announcement

The overall goal of the NIH Research Career Development program is to help ensure that a diverse pool of highly trained scientists are available in appropriate scientific disciplines to address the Nation's biomedical, behavioral, and clinical research needs. More information about Career programs may be found at the NIH Extramural Training Mechanisms website.

The objective of the NIH Mentored Research Scientist Development Award (K01) is to provide salary and research support for a sustained period of "protected time"• (3-5 years) for intensive research career development under the guidance of an experienced mentor, or sponsor, in the biomedical, behavioral or clinical sciences leading to research independence. The expectation is that through this sustained period of research career development and training, awardees will launch independent research careers and become competitive for new research project grant (e.g., R01) funding.

Although all of the participating NIH Institutes and Centers (ICs) use this mechanism to support career development experiences that lead to research independence, some ICs use the K01 award for individuals who propose to train in a new field or for individuals who have had a hiatus in their research career because of illness or pressing family circumstances. Other ICs utilize the K01 award to increase research workforce diversity by providing enhanced research career development opportunities.

Special Note: Applicants are cautioned that not all NIH Institutes and Centers (ICs) participate in this program, and that consultation with relevant IC staff prior to submission of an application is strongly encouraged. The participating ICs have different emphases and program requirements for this program. Therefore, a prospective applicant is urged to consult the Table of IC-Specific Information, Requirements and Staff Contacts to determine whether the planned research and training falls within the mission of one of the participating NIH ICs.

Eligible institutions and organizations: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Native American tribal organizations (other than Federally recognized tribal governments), and faith-based or community-based organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any candidate with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her mentor and organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. Multiple Principal Investigators are not allowed.

By the time of award, the individual must be a citizen or a non-citizen national of the United States or have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status. Individuals on temporary or student visas are not eligible.

Former principal investigators on NIH research project (R01), program project (P01), center grants, FIRST Awards (R29), sub-projects of program project (P01) or center grants, other career development awards (K- awards), or the equivalent are not eligible. Former principal investigators of an NIH Small Grant (R03), Exploratory/Developmental Grant (R21), Dissertation Awards (R36), or SBIR/STTR (R41, R42, R43, R44) remain eligible.

Candidates for this award must have a research or health-professional doctoral degree. Although all of the participating NIH ICs use this mechanism to support career development experiences that lead to research independence, some ICs use the K01 award for individuals who propose to train in a new field or for individuals who have had a hiatus in their research career because of illness or pressing family circumstances. Other ICs utilize the K01 award to increase research workforce diversity by providing enhanced research career development opportunities.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed. An individual may not have two or more competing NIH career development applications pending review concurrently. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Candidates may submit research project grant (RPG) applications concurrently with the K application. However, any concurrent RPG application may not duplicate the provisions of the career award application. K award recipients are encouraged to obtain funding from NIH or other Federal sources either as a PD/PI on a competing research grant award or cooperative agreement, or as project leader on a competing multi-project award as described in NOT-OD-08-065.

At the time of award, the candidate must have a "full-time" appointment at the academic institution that is the applicant institution. Candidates who have VA appointments may not consider part of the VA effort toward satisfying the "full time" requirement at the applicant institution. Candidates with VA appointments should contact the staff person in the relevant IC prior to preparing an application to discuss their eligibility. Under certain circumstances, an awardee may submit a written request to the awarding component requesting a reduction in minimum required percent effort, which will be considered on a case-by-case basis. Details on this policy are provided in NOT-OD-09-036.

Before submitting the application, the candidate must identify a mentor who will supervise the proposed career development and research experience. The mentor should be an active investigator in the area of the proposed research and be committed both to the career development of the candidate and to the direct supervision of the candidate's research. The mentor must document the availability of sufficient research support and facilities for high-quality research. Candidates are encouraged to identify more than one mentor, i.e., a mentoring team, if this is deemed advantageous for providing expert advice in all aspects of the research career development program. The mentor, or a member of the mentoring team, should have a successful track record of mentoring. In such cases, one individual must be identified as the principal mentor who will coordinate the candidate's research. The candidate must work with the mentor(s) in preparing the application.

The mentor(s) should describe the career development plan for the candidate (coordinated with the candidate's research strategy). The mentor and any co-mentors are also expected to provide an assessment of the candidate's qualifications and potential for a research career. The research environment and the availability and quality of needed research facilities and research resources (e.g., equipment, laboratory space, computer time, available research support, etc.) must also be described. The description should include items such as classes, seminars, and opportunities for interaction with other groups and scientists. Training in career skills, e.g. grant-writing and making effective presentations, is strongly encouraged.

The applicant institution must have a strong, well-established record of research and career development activities and faculty qualified to serve as mentors in biomedical, behavioral, or clinical research. The institution must demonstrate a commitment to the development of the candidate as a productive, independent investigator and be willing to allow the protected time needed by the candidate. The candidate, mentor(s), and institution must describe a research career development program that will maximize the use of this environment, including available facilities and resources.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-190.html.

INDEPENDENT SCIENTIST AWARD (PARENT K02): PA-11-191

Components of Participating Organizations

National Institutes of Health

National Heart, Lung, and Blood Institute

National Institute on Aging

National Institute on Alcohol Abuse and Alcoholism

National Institute of Allergy and Infectious Diseases

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Drug Abuse

National Institute on Deafness and Other Communication Disorders

National Institute of Dental and Craniofacial Research

National Institute of Environmental Health Sciences

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

Office of Dietary Supplements

Application Receipt/Submission Date(s): Multiple dates, see announcement

The overall goal of the NIH Research Career Development program is to help ensure that a diverse pool of highly trained scientists are available in appropriate scientific disciplines to address the Nation's biomedical, behavioral, and clinical research needs. More information about Career programs may be found at the NIH Extramural Training Mechanisms website.

The NIH Independent Scientist Award (K02) is intended to foster the development of outstanding scientists and enable them to expand their potential to make significant contributions to their field of research. It provides three, four, or five years of salary support and "protected time" for newly independent scientists who can demonstrate the need for a period of intensive research focus as a means of enhancing their research careers.

Candidates must hold a doctoral degree, independent peer reviewed research support at the time the award is made, and commit a minimum of 9 person-months (75% of full-time professional effort) conducting research and relevant career development activities during the period of the award. Depending on the sponsoring Institute or Center (IC), scientists whose work is primarily theoretical may apply for this award in the absence of external research grant support. Receipt of prior support may have an impact on eligibility for the K02 award. Each independent scientist career award program must be tailored to meet the individual needs of the candidate. The sponsoring institution must demonstrate a commitment to provide the environment, resources and the protected time required for the candidate to perform the activities included in the proposed research and career development plans.

Special Note: Applicants are cautioned that not all NIH Institutes and Centers (ICs) participate in this program, and that consultation with relevant IC staff prior to submission of an application is strongly encouraged. The participating ICs have different emphases and program requirements for this program. Therefore, a prospective applicant is urged to consult the Table of IC-Specific Information, Requirements and Staff Contacts to determine whether the planned research and training falls within the mission of one of the participating NIH ICs.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Native American tribal organizations (other than Federally recognized tribal governments), and faith-based or community-based organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any candidate with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. Multiple Principal Investigators are not allowed.

By the time of award, the individual must be a citizen or a non-citizen national of the United States or have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status). Individuals on temporary or student visas are not eligible.

Candidates for this award must have a doctoral degree and newly independent, peer-reviewed support at the time the award is made. Some of the participating NIH ICs require the candidate to have an NIH research grant at the time of application and that the support be from their IC. Other NIH ICs will accept candidates with peer-reviewed, independent research support from other sources.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed. An individual may not have two or more competing NIH career development applications pending review concurrently. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

At the time of award, the candidate must have a "full-time" appointment at the academic institution that is the applicant institution. Candidates who have VA appointments may not consider part of the VA effort toward satisfying the "full time"• requirement at the applicant institution. Candidates with VA appointments should contact the staff person in the relevant IC prior to preparing an application to discuss their eligibility. Under certain circumstances, an awardee may submit a written request to the awarding component requesting a reduction in minimum required percent effort, which will be considered on a case-by-case basis. Details on this policy are provided in NOT-OD-09-036.

Depending on the policies of the awarding IC, K02 awardees may apply for a one-time renewal for an additional three to five years of support if the K02 recipient continues to have independent peer-reviewed research support at the time of submission of the renewal application. Candidates should clearly demonstrate their continuing need for protected time to expand their research programs.

Depending on the policies of the sponsoring IC, candidates are expected to continue to hold independent peer-reviewed research support for the period of this award. Candidates losing this support during the award period must document in their annual Progress Reports efforts to replace this support and demonstrate that they continue to meet all other requirements of the K02 award.

The applicant institution must have a strong, well-established record of research and career development activities and faculty qualified in biomedical, behavioral, or clinical research to serve as mentors. The institution must demonstrate a commitment to the development of the candidate as a productive, independent investigator and be willing to allow the protected time needed by the candidate. The candidate, mentor, and institution must describe a research career development program that will maximize the use of this environment, including available facilities and resources.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-191.html.

ACADEMIC CAREER AWARD (PARENT K07): PA-11-192

Components of Participating Organizations

National Institutes of Health

National Center for Complementary and Alternative Medicine

National Institute on Aging

National Institute on Alcohol Abuse and Alcoholism

Office of Dietary Supplements

Application Receipt/Submission Date(s): Multiple dates, see announcement

The overall goal of the NIH Research Career Development program is to help ensure that a diverse pool of highly trained scientists are available in appropriate scientific disciplines to address the Nation's biomedical, behavioral, and clinical research needs. More information about Career programs may be found at the NIH Extramural Training Mechanisms website.

The objectives of the NIH Academic Career Award (K07) are to increase the pool of individuals with academic and research expertise in a specific area of biomedical research and to enhance the educational or research capacity at the grantee institution. This funding opportunity announcement (FOA) provides support for either of two types of activities:

  • K07 Development award: This award provides up to 5 years (a minimum of 3 years is required) of salary and research support for more junior investigators who are interested in developing academic and research expertise in a particular health-related field, as a way to increase the overall pool of individuals capable of research or teaching in the identified area. During the period of the award, the candidate will become a successful academic researcher in the chosen area. Research, teaching, and leadership skills are to be learned during the tenure of the award. Curriculum building skills are encouraged. A mentor is required. A minimum of 9 person months (75%) of full-time professional effort is required annually; the remainder may be devoted to other research related and/or teaching pursuits consonant with the objectives of the award.

  • K07 Leadership award: This award provides support for up to 5 years (a minimum of 2 years is required) for more senior investigators who are interested in improving the curricula and enhancing the health-related research capacity within an academic institution. The Leadership candidate must have acknowledged scientific expertise and leadership skills and sufficient clinical training, research, or teaching experience in the academic area of interest to an NIH awarding component to implement a program of curriculum development within the sponsoring institution. It is expected that support under this award will increase the visibility and the overall research support or academic capacity for the given field of research within the academic medical/health and research community. At least 3 person months (25%) but not more than 6 person months (50%) of full-time professional effort must be devoted to the program annually.

  • Development and Leadership awards are not renewable nor are they transferable from one PD/PI to another. Because the objectives of the K07 award are to increase the pool of individuals in academia and/or to implement or enhance curriculum development within the sponsoring institution, awards are not transferable to another institution. Only in exceptional circumstances would consideration be given for the transfer of a Development award.

Special Note: Applicants are cautioned that not all NIH Institutes and Centers (ICs) participate in this program, and that consultation with relevant IC staff prior to submission of an application is strongly encouraged. The participating ICs have different emphases and program requirements for this program. Therefore, a prospective applicant is urged to consult the Table of IC-Specific Information, Requirements and Staff Contacts to determine whether the planned research and training falls within the mission of one of the participating NIH ICs.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Native American tribal organizations (other than Federally recognized tribal governments), and faith-based or community-based organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any candidate with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/hermentor (relevant to the Development award) and organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. Multiple Principal Investigators are not allowed.

By the time of award, the individual must be a citizen or a non-citizen national of the United States or have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status). Individuals on temporary or student visas are not eligible.

Candidates for this award must have a clinical, research, or health-professional doctoral degree. Such degrees include but are not limited to the Ph.D., M.D., D.O., D.D.S., D.M.D., O.D., D.C., D.S.W., D.P.H., Pharm.D., N.D. (Doctor of Naturopathy), as well as a doctoral degree in nursing research or practice.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed. An individual may not have two or more competing NIH career development applications pending review concurrently. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Candidates may submit research project grant (RPG) applications concurrently with the K application. However, any concurrent RPG application may not duplicate the provisions of the career award application. K award recipients are encouraged to obtain funding from NIH or other Federal sources either as a PD/PI on a competing research grant award or cooperative agreement or as project leader on a competing multi-project award as described in NOT-OD-08-065.

K07 Development:

  • Former PD/PIs of NIH Small Grants (R03) or Exploratory/Developmental Grants (R21) remain eligible for a Development award.

  • Individuals are not eligible for a Development Award if: (1) they have been a PD/PI or have an application pending for any other PHS career award (e.g., K01, K08, K22, K23, K25, K99/R00); or (2) if they are a current or former PD/PIs on NIH research project grants (e.g. R01), project leaders on sub-projects of program project (P01) or center (P50) grants; or (3) if they are PD/PI on an equivalent non-PHS peer-reviewed research grants that are over $100,000 direct costs per year. Candidates are encouraged to contact the awarding IC staff for further guidance.

  • Candidates must identify a mentor(s) with extensive and appropriate research experience for the proposed research development plan.

  • The sponsoring institution must provide a statement of commitment to the proposed level of effort required by this award.

K07 Leadership:

  • Candidates may identify appropriate collaborator(s) from the relevant disciplines who will agree to collaborate on the development of the course(s) and curricula.

  • Candidates may not use the Leadership Award to support the awardee's clinical practice, professional consultation or other comparable activities, except when such activities are required by the objectives of this program.

  • The sponsoring institution must provide a statement of commitment to the proposed level of effort required by this award; and describe a plan for relieving the candidate from administrative/clinical responsibilities to achieve the required effort commitment

  • The sponsoring institution must provide a statement (plan) demonstrating a commitment to the further development and implementation of courses or curriculum resulting from the Leadership award.

At the time of award, the candidate must have a "full-time"• appointment at the academic institution that is the applicant institution. Candidates who have VA appointments may not consider part of the VA effort toward satisfying the "full time"• requirement at the applicant institution. Candidates with VA appointments should contact the staff person in the relevant IC prior to preparing an application to discuss their eligibility. Under certain circumstances, an awardee may submit a written request to the awarding component requesting a reduction in minimum required percent effort, which will be considered on a case-by-case basis. Details on this policy are provided in NOT-OD-09-036.

Candidates for a Development award must be able to commit a minimum of 9 person months (75%) of full-time professional effort to conducting research career development and research activities associated with this award. The remaining 3 person months (25%) effort can be divided among other research, clinical and teaching activities only if these activities are in a fashion consistent with the goals of the K07 award, i.e., the candidate's development into an independent investigator.

Candidates for a Leadership award must be able to devote from 3-6 person-months (25-50% full-time professional effort) to the program, a portion of which may include research.

Before submitting the application, the candidate for a Development award must identify a mentor who will supervise the proposed career development and research experience. The mentor should be an active investigator in the area of the proposed research and be committed both to the career development of the candidate and to the direct supervision of the candidate's research. The mentor must document the availability of sufficient research support and facilities for high-quality research. Candidates are encouraged to identify more than one mentor, i.e., a mentoring team, if this is deemed advantageous for providing expert advice in all aspects of the research career development program. The mentor, or a member of the mentoring team, should have a successful track record of mentoring. In such cases, one individual must be identified as the principal mentor who will coordinate the candidate's research. The candidate must work with the mentor(s) in preparing the application.

The mentor(s) should describe the career development plan for the candidate (coordinated with the candidate's research strategy). The mentor and any co-mentors are also expected to provide an assessment of the candidate's qualifications and potential for a research career. The research environment and the availability and quality of needed research facilities and research resources (e.g., equipment, laboratory space, computer time, available research support, etc.) must also be described. The description should include items such as classes, seminars, and opportunities for interaction with other groups and scientists. Training in career skills, e.g. grant-writing and making effective presentations, is strongly encouraged.

The applicant institution must have a strong, well-established record of career development activities and faculty qualified to serve as mentors in biomedical, behavioral, or clinical research. The institution must demonstrate a commitment to the development of the candidate as a productive investigator and be willing to allow the protected time needed by the candidate. The candidate, mentor(s), and institution must describe a career development program that will maximize the use of this environment, including available facilities and resources.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-192.html.

MENTORED CLINICAL SCIENTIST RESEARCH CAREER DEVELOPMENT AWARD (PARENT K08): PA-11-193

Components of Participating Organizations

National Institutes of Health

National Center for Complementary and Alternative Medicine

National Cancer Institute

National Eye Institute

National Heart, Lung, and Blood Institute

National Institute on Aging

National Institute on Alcohol Abuse and Alcoholism

National Institute of Allergy and Infectious Diseases

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Institute of Biomedical Imaging and Bioengineering

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Drug Abuse

National Institute on Deafness and Other Communication Disorders

National Institute of Dental and Craniofacial Research

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Environmental Health Sciences

National Institute of General Medical Sciences

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

Office of Dietary Supplements

Application Receipt/Submission Date(s): Multiple dates, see announcement

The overall goal of the NIH Research Career Development program is to help ensure that a diverse pool of highly trained scientists are available in appropriate scientific disciplines to address the Nation's biomedical, behavioral, and clinical research needs. More information about Career programs may be found at the NIH Extramural Training Mechanisms website.

The objective of the NIH Mentored Clinical Scientist Research Career Development Award (K08) program is to provide salary and research support for a sustained period of "protected time"• (3-5 years) to support didactic study and/or mentored research for individuals with clinical doctoral degrees (e.g., M.D., D.D.S., D.M.D., D.O., D.C., O.D., N.D., D.V.M., Pharm.D., or Ph.D. in clinical disciplines). The K08 provides support for an intensive, mentored research career development experience in biomedical or behavioral research, including translational research leading to research independence. For the purpose of this award, translational research is defined as application of basic research discoveries toward the diagnosis, management, and prevention of human disease. Individuals with a clinical doctoral degree interested in pursuing a career in patient-oriented research should refer to the NIH Mentored Patient Oriented Research Career Development Award (Parent K23).

The K08 award may be used by candidates with different levels of prior research training and at different stages in their career development. For example, a candidate with limited experience in a given field of research may use an award to support a career development experience that includes a designated period of didactic training followed by a period of closely supervised research experience. A candidate with previous research experience and training may not require extensive additional didactic preparation, and may use an award to support a career development experience that focuses on an intensive, supervised research experience.

Special Note: Applicants are cautioned that not all NIH Institutes and Centers (ICs) participate in this program, and that consultation with relevant IC staff prior to submission of an application is strongly encouraged. The participating ICs have different emphases and program requirements for this program. Therefore, a prospective applicant is urged to consult the Table of IC-Specific Information, Requirements and Staff Contacts to determine whether the planned research and training falls within the mission of one of the participating NIH ICs.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Native American tribal organizations (other than Federally recognized tribal governments), and faith-based or community-based organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any candidate with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her mentor and organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. Multiple Principal Investigators are not allowed.

By the time of award, the individual must be a citizen or a non-citizen national of the United States or have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status). Individuals on temporary or student visas are not eligible.

Former PD/PIs on NIH research project (R01), program project (P01), center grants, FIRST Awards (R29), sub-projects of program project (P01) or center grants, other career development awards (K- awards), or the equivalent are not eligible. Former principal investigators of an NIH Small Grant (R03), Exploratory/Developmental Grant (R21), Dissertation Awards (R36), or SBIR/STTR (R41, R42, R43, R44) remain eligible.

Candidates for this award must have a clinical doctoral degree. Such degrees include but are not limited to the M.D., D.O., D.D.S., D.M.D., O.D., D.C., Pharm.D., N.D. (Doctor of Naturopathy), D.V.M. Individuals with the Ph.D. or other doctoral degree in clinical disciplines such as clinical psychology, nursing, clinical genetics, speech-language pathology, audiology or rehabilitation are also eligible. Individuals holding the Ph.D. in a non-clinical discipline who are certified to perform clinical duties should contact the appropriate Institute concerning their eligibility for a K08 award.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed. An individual may not have two or more competing NIH career development applications pending review concurrently. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Candidates may submit research project grant (RPG) applications concurrently with the K application. However, any concurrent RPG application may not duplicate the provisions of the career award application. K award recipients are encouraged to obtain funding from NIH or other Federal sources either as a PD/PI on a competing research grant award or cooperative agreement or as project leader on a competing multi-project award as described in NOT-OD-08-065.

At the time of award, the candidate must have a "full-time" appointment at the academic institution that is the applicant institution. Candidates who have VA appointments may not consider part of the VA effort toward satisfying the "full time"• requirement at the applicant institution. Candidates with VA appointments should contact the staff person in the relevant IC prior to preparing an application to discuss their eligibility. Under certain circumstances, an awardee may submit a written request to the awarding component requesting a reduction in minimum required percent effort, which will be considered on a case-by-case basis. Details on this policy are provided in NOT-OD-09-036.

Before submitting the application, the candidate must identify a mentor who will supervise the proposed career development and research experience. The mentor should be an active investigator in the area of the proposed research and be committed both to the career development of the candidate and to the direct supervision of the candidate's research. Candidates are encouraged to identify more than one mentor, i.e., a mentoring team, if this is deemed advantageous for providing expert advice in all aspects of the research career development program. The mentor must document the availability of sufficient research support and facilities for high-quality research. The mentor, or a member of the mentoring team, should have a successful track record of mentoring. In such cases, one individual must be identified as the principal mentor who will coordinate the candidate's research. The candidate must work with the mentor(s) in preparing the application.

The mentor(s) should describe the career development plan for the candidate (coordinated with the candidate's research strategy). The mentor and any co-mentors are also expected to provide an assessment of the candidate's qualifications and potential for a research career. The research environment and the availability and quality of needed research facilities and research resources (e.g., equipment, laboratory space, computer time, available research support, etc.) must also be described. The description should include items such as classes, seminars, and opportunities for interaction with other groups and scientists. Training in career skills, e.g. grant-writing and making effective presentations, is strongly encouraged.

The applicant institution must have a strong, well-established record of career development activities and faculty qualified to serve as mentors in biomedical, behavioral, or clinical research. The institution must demonstrate a commitment to the development of the candidate as a productive investigator and be willing to allow the protected time needed by the candidate. The candidate, mentor(s), and institution must describe a career development program that will maximize the use of this environment, including available facilities and resources.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-193.html.

MENTORED PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AWARD (PARENT K23): PA-11-194

Components of Participating Organizations

National Institutes of Health

National Center for Complementary and Alternative Medicine

National Cancer Institute

National Eye Institute

National Heart, Lung, and Blood Institute

National Institute on Aging

National Institute on Alcohol Abuse and Alcoholism

National Institute of Allergy and Infectious Diseases

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Institute of Biomedical Imaging and Bioengineering

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Drug Abuse

National Institute on Deafness and Other Communication Disorders

National Institute of Dental and Craniofacial Research

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Environmental Health Sciences

National Institute of General Medical Sciences

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

National Institute of Nursing Research

Office of Dietary Supplements

Application Receipt/Submission Date(s): Multiple dates, see announcement

The overall goal of the NIH Research Career Development program is to help ensure that a diverse pool of highly trained scientists are available in appropriate scientific disciplines to address the Nation's biomedical, behavioral, and clinical research needs. More information about Career programs may be found at the NIH Extramural Training Mechanisms website.

The objective of the NIH Mentored Patient-Oriented Research Career Development Award (K23) program is to provide salary and research support for a sustained period of "protected time" (3-5 years) to ensure a future cadre of well-trained scientists working in Patient-Oriented Research (POR) who will become competitive for NIH research project (R01) grant support. The specific objectives of the Mentored Patient-Oriented Research Career Development Award are to:

  • Encourage research-oriented clinicians to develop independent research skills and gain experience in advanced methods and experimental approaches needed to become an independent investigator conducting patient-oriented research.

  • Increase the pool of clinical researchers who can conduct patient-oriented studies, capitalizing on the discoveries of biomedical research and translating them to clinical settings.

  • Support the career development of investigators who have made a commitment to focus their research endeavors on patient-oriented research.

  • For the purposes of the K23 award, Patient-Oriented Research is defined as research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator directly interacts with human subjects. This area of research includes: 1) mechanisms of human disease; 2) therapeutic interventions; 3) clinical trials; and 4) the development of new technologies. Studies falling under Exemption 4 for human subjects research are not included in this definition. See also the NIH Director's Panel on Clinical Research Report.

Special Note: Applicants are cautioned that not all NIH Institutes and Centers (ICs) participate in this program, and that consultation with relevant IC staff prior to submission of an application is strongly encouraged. The participating ICs have different emphases and program requirements for this program. Therefore, a prospective applicant is urged to consult the Table of IC-Specific Information, Requirements and Staff Contacts to determine whether the planned research and training falls within the mission of one of the participating NIH ICs.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Native American tribal organizations (other than Federally recognized tribal governments), and faith-based or community-based organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any candidate with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her mentor and organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. Multiple Principal Investigators are not allowed.

By the time of award, the individual must be a citizen or a non-citizen national of the United States or have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status). Individuals on temporary or student visas are not eligible.

Former PD/PIs on NIH research project (R01), program project (P01), center grants, FIRST Awards (R29), sub-projects of program project (P01) or center grants, other career development awards (K-awards), or the equivalent are not eligible. Former PD/PIs of an NIH Small Grant (R03), Exploratory/Developmental Grant (R21), Dissertation Awards (R36), or SBIR/STTR (R41, R42, R43, R44) remain eligible.

Candidates for this award must have a health-professional doctoral degree. Such degrees include but are not limited to the M.D., D.O., D.D.S., D.M.D., O.D., D.C., Pharm.D., N.D. (Doctor of Naturopathy), as well as a doctoral degree in nursing research or practice. Candidates with Ph.D. degrees are eligible for this award if the degree is in a clinical field and they usually perform clinical duties. Individuals with the Ph.D. or other doctoral degree in clinical disciplines such as clinical psychology, clinical genetics, speech-language pathology, audiology or rehabilitation are also eligible. Individuals holding the Ph.D. in a non-clinical discipline but who are certified to perform clinical duties should contact the appropriate Institute concerning their eligibility for a K23 award. Candidates also must have completed their clinical training, including specialty and, if applicable, subspecialty training prior to receiving an award. However, candidates may submit an application prior to the completion of clinical training.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed. An individual may not have two or more competing NIH career development applications pending review concurrently. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Candidates may submit research project grant (RPG) applications concurrently with the K application. However, any concurrent RPG application may not duplicate the provisions of the career award application. K award recipients are encouraged to obtain funding from NIH or other Federal sources either as a PD/PI on a competing research grant award or cooperative agreement or as project leader on a competing multi-project award as described in NOT-OD-08-065.

At the time of award, the candidate must have a "full-time" appointment at the academic institution that is the applicant institution. Candidates who have VA appointments may not consider part of the VA effort toward satisfying the "full time" requirement at the applicant institution. Candidates with VA appointments should contact the staff person in the relevant IC prior to preparing an application to discuss their eligibility. Under certain circumstances, an awardee may submit a written request to the awarding component requesting a reduction in minimum required percent effort, which will be considered on a case-by-case basis. Details on this policy are provided in NOT-OD-09-036.

Before submitting the application, the candidate must identify a mentor who will supervise the proposed career development and research experience. The mentor should be an active investigator in the area of the proposed research and be committed both to the career development of the candidate and to the direct supervision of the candidate's research. The mentor must document the availability of sufficient research support and facilities for high-quality research. Candidates are encouraged to identify more than one mentor, i.e., a mentoring team, if this is deemed advantageous for providing expert advice in all aspects of the research career development program. The mentor, or a member of the mentoring team, should have a successful track record of mentoring. In such cases, one individual must be identified as the principal mentor who will coordinate the candidate's research. The candidate must work with the mentor(s) in preparing the application.

The mentor(s) should describe the career development plan for the candidate (coordinated with the candidate's research strategy). The mentor and any co-mentors are also expected to provide an assessment of the candidate's qualifications and potential for a research career. The research environment and the availability and quality of needed research facilities and research resources (e.g., equipment, laboratory space, computer time, available research support, etc.) must also be described. The description should include items such as classes, seminars, and opportunities for interaction with other groups and scientists. Training in career skills, e.g. grant-writing and making effective presentations, is strongly encouraged.

The applicant institution must have a strong, well-established record of career development activities and faculty qualified to serve as mentors in biomedical, behavioral, or clinical research. The institution must demonstrate a commitment to the development of the candidate as a productive investigator and be willing to allow the protected time needed by the candidate. The candidate, mentor(s), and institution must describe a career development program that will maximize the use of this environment, including available facilities and resources.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-194.html.

MIDCAREER INVESTIGATOR AWARD IN PATIENT-ORIENTED RESEARCH (PARENT K24): PA-11-195

Components of Participating Organizations

National Institutes of Health

National Center for Complementary and Alternative Medicine

National Cancer Institute

National Heart, Lung, and Blood Institute

National Institute on Aging

National Institute on Alcohol Abuse and Alcoholism

National Institute of Allergy and Infectious Diseases

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Drug Abuse

National Institute on Deafness and Other Communication Disorders

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Environmental Health Sciences

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

National Institute of Nursing Research

Office of Dietary Supplements

Application Receipt/Submission Date(s): Multiple dates, see announcement

The overall goal of the NIH Research Career Development program is to help ensure that a diverse pool of highly trained scientists are available in appropriate scientific disciplines to address the Nation's biomedical, behavioral, and clinical research needs. More information about Career programs may be found at the NIH Extramural Training Mechanisms website.

The NIH Midcareer Investigator Award in Patient-Oriented Research (K24) award is designed to enable mid-career clinician scientists to:

  • Devote more time to augment their capabilities in Patient-Oriented Research (POR); and

  • Provide mentoring to new clinical investigators in the conduct of POR (see below for definition).

  • The K24 award is intended to provide protected time to mid-career clinical investigators who are typically at the Associate Professor level or the equivalent (see Section III, Eligible Individuals) and who have their own independent peer-reviewed research support to provide mentoring to junior clinical investigators, particularly K23 grantees, in POR and to stabilize the careers of these investigators so that they could continue to conduct POR and be available as mentors in POR. A K24 award recipient who continues to have an independent peer-reviewed patient-oriented research program and continues to provide mentoring to new investigators can continue to contribute to the overall goals of the program after being promoted to Full Professor. This award has formed an important part of the NIH initiative to attract and retain talented individuals to the challenges of patient-oriented research. The overall goal is to increase the pool of clinical researchers who can conduct patient-oriented research, who will be able to successfully compete for peer-reviewed grants, and who will mentor the next generation of clinical investigators.

  • It is expected that K24 recipients will obtain new or additional independent peer-reviewed funding for POR as PD/PI and establish and assume leadership roles in collaborative POR programs. In addition, it is expected that there will be an increased effort and commitment to act as a mentor to beginning clinician investigators in POR to enhance the research productivity of both the K24 investigator and increase the pool of well-trained clinical researchers of the future.

  • For the purposes of this award, Patient-Oriented Research is defined as research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator directly interacts with human subjects. This area of research includes: 1) mechanisms of human disease; 2) therapeutic interventions; 3) clinical trials; and 4) the development of new technologies. Studies falling under Exemption 4 for human subjects research are not included in this definition. See also the NIH Directors Panel on Clinical Research Report.

Special Note: Applicants are cautioned that not all NIH Institutes and Centers (ICs) participate in this program, and that consultation with relevant IC staff prior to submission of an application is strongly encouraged. The participating ICs have different emphases and program requirements for this program. Therefore, a prospective applicant is urged to consult the Table of IC-Specific Information, Requirements and Staff Contacts to determine whether the planned research and training falls within the mission of one of the participating NIH ICs.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Native American tribal organizations (other than Federally recognized tribal governments), and faith-based or community-based organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any candidate with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. Multiple Principal Investigators are not allowed.

By the time of award, the individual must be a citizen or a non-citizen national of the United States or have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status). Individuals on temporary or student visas are not eligible.

Candidates for this award must have a health-professional doctoral degree or its equivalent. Such degrees include but are not limited to the M.D., D.O., D.D.S., D.M.D., O.D., D.C., Pharm.D., N.D. (Doctor of Naturopathy), as well as a doctoral degree in nursing. Candidates with Ph.D. degrees are eligible for this award if the degree is in a clinical field or they perform patient-oriented research (POR). This may include clinical psychologists, clinical geneticists, speech and language pathologists.

Candidates should typically be in the midcareer stage at the Associate Professor level or functioning at that rank in an academic setting or equivalent non-academic setting and must have an established record of independent, peer-reviewed patient-oriented research grant funding including at the time of application and record of publications. This award is intended for individuals who have a record of supervising and mentoring patient-oriented researchers. A K24 award recipient who is promoted to Full Professor, but continues to have an independent peer-reviewed patient-oriented research program and provides mentoring to new investigators, may continue to be supported through the K24 program.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed. An individual may not have two or more competing NIH career development applications pending review concurrently. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Candidates must be able to demonstrate the need for protected time, 3-6 person months (25-50% of full-time professional effort) for a period of intensive research focus as a means of augmenting their capabilities in POR and act as a mentor to new clinical investigators in the conduct of POR during this period. Candidates for the K24 award may not have pending peer review or concurrently apply for any other PHS career award.

Depending on the policies of the awarding IC, K24 awardees may apply for a one-time renewal for an additional three to five years of support if the K24 recipient continues to have independent peer-reviewed research support at the time of submission of the renewal application. Candidates should clearly demonstrate their continuing need for protected time to expand their research programs and to serve as mentors to more junior POR researchers.

Depending on the policies of the sponsoring IC, candidates are expected to continue to hold independent peer-reviewed research support for the period of this award. Candidates losing this support during the award period must document in their annual Progress Reports efforts to replace this support and demonstrate that they continue to meet all other requirements of the K24 award.

The institution must be able to demonstrate a commitment to the candidate as a productive, independent investigator. The application must describe a program that will use the relevant research and educational resources and facilities available. The institution must certify that the candidate will be released from other duties and be able to devote between 3-6 person-months (25 to 50% full-time professional effort) to a patient-oriented research program. The applicant institution must document the availability of beginning clinical investigators (including junior clinical faculty) to be mentored. In addition, if there is an NIH institutional career development award (K12); an NIH Clinical Translational Science Award (CTSA) with an institutional career development component; or an NIH Clinical Research Curriculum Award (K30) at the sponsoring institution, a plan should be described for integrating the proposed K24 mentoring activities with activities under these programs.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-195.html.

MENTORED QUANTITATIVE RESEARCH DEVELOPMENT AWARD (PARENT K25): PA-11-196

Components of Participating Organizations

National Institutes of Health

National Cancer Institute

National Human Genome Research Institute

National Heart, Lung, and Blood Institute

National Institute of Allergy and Infectious Diseases

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Institute of Biomedical Imaging and Bioengineering

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Drug Abuse

National Institute on Deafness and Other Communication Disorders

National Institute of Dental and Craniofacial Research

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Environmental Health Sciences

National Institute of General Medical Sciences

National Institute of Neurological Disorders and Stroke

Office of Dietary Supplements

Application Receipt/Submission Date(s): Multiple dates, see announcement

The overall goal of the NIH Research Career Development program is to help ensure that a diverse pool of highly trained scientists are available in appropriate scientific disciplines to address the Nation's biomedical, behavioral, and clinical research needs. More information about Career programs may be found at the NIH Extramural Training Mechanisms website.

A particular area of research is often invigorated by novel perspectives that may be provided by individuals trained outside that research arena. In an effort to advance research relevant to the mission of the National Institutes of Health (NIH), which includes basic biomedical, clinical biomedical, bioengineering, bioimaging, and behavioral research, the participating Institutes and Centers (ICs) encourage applications for the NIH Mentored Quantitative Research Career Development Award (K25). The K25 mechanism is meant to attract to NIH-relevant research those investigators whose quantitative science and engineering research has thus far not been focused primarily on questions of health and disease. Examples of quantitative scientific and technical backgrounds considered appropriate for this award include, but are not limited to: mathematics, statistics, economics, computer science, imaging science, informatics, physics, chemistry, and engineering.

The NIH is especially interested in increasing the number of scientists trained to conduct high-quality research that combines insights derived from, and cuts across, different scientific, technical, and biomedical areas. Accordingly, the K25 award forms an important part of an initiative to attract talented individuals with highly-developed quantitative skills to the challenges of research relevant to the mission of NIH. The K25 award is intended to increase the availability of high-quality, multidisciplinary, didactic training and research project guidance, in the context of a mentored research career transition experience. Candidates interested in cross-disciplinary research will become well-grounded in behavioral, biomedical, bioimaging, or bioengineering research. At the completion of the award, candidates should have both the knowledge and the skills necessary to compete for independent research support from NIH, or to participate as leading members of multi-disciplinary research teams.

The specific objectives of the K25 award are to:

  • Encourage research-oriented quantitative scientists and engineers with little or no experience in biomedicine, bioengineering, bioimaging, or behavioral research to gain fundamental knowledge in these areas and develop relevant research skills, and to gain experience in current concepts, advanced methods, and experimental approaches that will allow them to conduct basic or clinical biomedical, behavioral, bioimaging, or bioengineering research, and to become independent investigators or play leading roles in multi-disciplinary research teams.

  • Increase the pool of quantitative researchers who can conduct biomedical, behavioral, or bioengineering studies, capitalizing on the quantitative backgrounds of these investigators to inform new directions in biomedical, behavior and bioengineering research.

  • Provide a unique opportunity for candidates holding degrees in quantitative science or engineering to embark on three to five years of special study, including course work, seminars, meetings, and mentored research, to achieve the career enhancement goals outlined above.

  • Because of the focus on a progression toward independence as a quantitative biomedical, behavioral, bioimaging, or bioengineering researcher, the prospective candidate for the Mentored Quantitative Research Career Development Award will require enhanced skills in the experimental, theoretical and conceptual approaches used in biomedicine, behavioral science, bioimaging or bioengineering. To satisfy this requirement, the candidate should propose a period of study and career development that is complementary to his or her previous research and experience. For example, a candidate with no or very limited experience in a given field of biomedical research may find a phased developmental program lasting for five years that includes a designated period of didactic training together with a closely supervised research experience the most efficient means of attaining independence. A candidate with, for example, more research experience in biomedicine may benefit from a program with greater emphasis on appropriate laboratory research with lower levels of supervision and direction. All programs should be carefully tailored to meet the individual needs of the candidate and must include (an) active mentor(s) who is (are) competent and willing to provide the appropriate research guidance. Candidates should strongly consider incorporating into their training plan formal courses in relevant areas of biomedicine, behavioral science, bioimaging, or bioengineering; this program offers a unique opportunity to devote protected time to this activity.

Special Note: Applicants are cautioned that not all NIH Institutes and Centers (ICs) participate in this program, and that consultation with relevant IC staff prior to submission of an application is strongly encouraged. The participating ICs have different emphases and program requirements for this program. Therefore, a prospective applicant is urged to consult the Table of IC-Specific Information, Requirements and Staff Contacts to determine whether the planned research and training falls within the mission of one of the participating NIH ICs.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Native American tribal organizations (other than Federally recognized tribal governments), and faith-based or community-based organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any candidate with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her mentor and organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. Multiple Principal Investigators are not allowed.

By the time of award, the individual must be a citizen or a non-citizen national of the United States or have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status). Individuals on temporary or student visas are not eligible.

Former principal investigators on NIH research project (R01), program project (P01), center grants, FIRST Awards (R29), sub-projects of program project (P01) or center grants, other career development awards (K- awards), or the equivalent are not eligible. Former principal investigators of an NIH Small Grant (R03), Exploratory/Developmental Grant (R21), Dissertation Awards (R36), or SBIR/STTR (R41, R42, R43, R44) remain eligible.

Candidates must have an advanced degree in a quantitative area of science or engineering (M.S.E.E., Ph.D., D.Sc., etc.) and have demonstrated research interests in their primary quantitative discipline. The candidate should have demonstrated professional accomplishments consonant with his or her career status, and should have demonstrated experience or interest in pursuing research (including research outside of biomedicine, behavior, bioimaging, or bioengineering).

The award is intended for research-oriented investigators at any level of experience, from the postdoctoral level to senior faculty level, who have shown clear evidence of productivity and research excellence in the field of their training, and who would like to expand their research capability, with the goal of making significant contributions to behavioral, biomedical (basic or clinical), bioimaging or bioengineering research that is relevant to the NIH mission.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed. An individual may not have two or more competing NIH career development applications pending review concurrently. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Candidates may submit research project grant (RPG) applications concurrently with the K application. However, any concurrent RPG application may not duplicate the provisions of the career award application. K award recipients are encouraged to obtain funding from NIH or other Federal sources either as a PD/PI on a competing research grant award or cooperative agreement, or as project leader on a competing multi-project award as described in NOT-OD-08-065.

At the time of award, the candidate must have a "full-time"• appointment at the academic institution that is the applicant institution. Candidates who have VA appointments may not consider part of the VA effort toward satisfying the "full time"• requirement at the applicant institution. Candidates with VA appointments should contact the staff person in the relevant IC prior to preparing an application to discuss their eligibility. Under certain circumstances, an awardee may submit a written request to the awarding component requesting a reduction in minimum required percent effort, which will be considered on a case-by-case basis. Details on this policy are provided in NOT-OD-09-036.

Before submitting the application, the candidate must identify a mentor who will supervise the proposed career development and research experience. The mentor should be an active investigator in the area of the proposed research and be committed both to the career development of the candidate and to the direct supervision of the candidate's research. The mentor must document the availability of sufficient research support and facilities for high-quality research. Candidates are encouraged to identify more than one mentor, i.e., a mentoring team, if this is deemed advantageous for providing expert advice in all aspects of the research career development program. The mentor, or a member of the mentoring team, should have a successful track record of mentoring. In such cases, one individual must be identified as the principal mentor who will coordinate the candidate's research. The candidate must work with the mentor(s) in preparing the application.

The mentor(s) should describe the career development plan for the candidate (coordinated with the candidate's research strategy). The mentor and any co-mentors are also expected to provide an assessment of the candidate's qualifications and potential for a research career. The research environment and the availability and quality of needed research facilities and research resources (e.g., equipment, laboratory space, computer time, available research support, etc.) must also be described. The description should include items such as classes, seminars, and opportunities for interaction with other groups and scientists. Training in career skills, e.g., grant-writing and making effective presentations, is strongly encouraged.

The institution must have a strong, well-established research and biomedical, behavioral, or bioengineering career development program, or have demonstrable ties to such programs. For example, if the mentor is based in industry and the career development program requires didactic activities at a nearby university, access to such activities must be described. The institution must demonstrate a commitment to the development of the candidate as a productive investigator and be willing to allow the protected time needed by the candidate. The institution must also propose qualified faculty as mentors in the specific research area. It is anticipated that a K25 awardee will apply for independent funding during the latter period of this award, and that the sponsoring institution will provide the resources required for them to do so.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-196.html.

NIH PATHWAY TO INDEPENDENCE AWARD (PARENT K99/R00): PA-11-197

Components of Participating Organizations

National Institutes of Health

National Center for Complementary and Alternative Medicine

National Cancer Institute

National Center for Research Resources

National Eye Institute

National Human Genome Research Institute

National Heart, Lung, and Blood Institute

National Institute on Aging

National Institute on Alcohol Abuse and Alcoholism

National Institute of Allergy and Infectious Diseases

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Institute of Biomedical Imaging and Bioengineering

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Drug Abuse

National Institute on Deafness and Other Communication Disorders

National Institute of Dental and Craniofacial Research

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Environmental Health Sciences

National Institute of General Medical Sciences

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

National Institute of Nursing Research

National Library of Medicine

Office of Dietary Supplements

Application Receipt/Submission Date(s): Multiple dates, see announcement

The overall goal of the NIH Research Career Development program is to help ensure that a diverse pool of highly trained scientists are available in appropriate scientific disciplines to address the Nation's biomedical, behavioral, and clinical research needs. More information about Career programs may be found at the NIH Extramural Training Mechanisms website.

The objective of the NIH Pathway to Independence Award (K99/R00) initiative is to assist postdoctoral investigators in transitioning to a stable independent research position with NIH or other independent research funding. One of the most challenging transitions in any research career is the transition from postdoctoral trainee to independent scientist. Reports from the National Research Council of the National Academies of Science (Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research, and Advancing the Nation's Health Needs: NIH Research Training Programs) have highlighted the need for enhanced efforts to foster the transition of postdoctoral scientists from mentored environments to independence.

NIH believes that the creativity and innovation of new independent investigators in their early career stages play an integral role in addressing our Nation's biomedical, behavioral, and clinical research needs. However, the average age of first-time (new) Program Director/Principal Investigators (PD/PI) obtaining R01 research funding from the NIH has risen to 42 years for Ph.D. degree holders and 44 years for M.D. and M.D./Ph.D. degree holders. The intent of the K99/R00 program is to help alleviate this trend and to assist new investigators in transitioning to stable independent research positions at an earlier age and with an enhanced probability of success in obtaining independent NIH or other independent research support.

In addition to this initiative, NIH Institutes and Centers (ICs) support a variety of other mentored career development programs designed to foster the transition of new investigators to research independence, which may be more suitable for particular candidates. Information describing all NIH Career Development Award programs can be found at the K Kiosk - Information about NIH Career Development Awards.

The K99/R00 award will provide up to 5 years of support consisting of two phases. The initial mentored phase will provide support for up to 2 years for the most promising and exceptionally talented new investigators who have no more than 5 years of postdoctoral research training experience at the time of initial application or subsequent resubmission(s) and do not already have a full-time tenure track assistant professor position (or equivalent). This initial phase of mentored support will allow the candidate time to obtain additional training, complete research, publish results, and bridge to an independent research position. The candidate must propose a research project that will be pursued during the K99 phase and transition into an independent project during the R00 phase of the award. The candidate and mentor(s) together will be responsible for all aspects of the mentored (K99 phase) career development and research program. An individual may submit an application from an extramural or intramural sponsoring institution/organization that has a rich and extensive research program in the area of interest as well as the faculty, facilities and resources to support the proposed research endeavor. The individual must select an appropriate mentor with a track record of funded research related to the selected research topic and experience as a supervisor and mentor. The sponsoring institution must ensure that the candidate has the protected time needed to conduct the proposed research.

Following the mentored phase, the individual may request up to 3 years of support to conduct research as an independent scientist at an extramural sponsoring institution/organization to which the individual has been recruited, been offered and has accepted a tenure-track full-time assistant professor position (or equivalent). This support is to allow the individual to continue to work toward establishing his/her own independent research program and prepare an application for regular research grant support (R01). Support for the independent phase, however, is not automatic and is contingent upon being accepted by an appropriate extramural institution and the successful NIH programmatic review of the individual's mentored phase of the award.

Special Note: Applicants are cautioned that not all NIH Institutes and Centers (ICs) participate in this program, and that consultation with relevant IC staff prior to submission of an application is strongly encouraged. The participating ICs have different emphases and program requirements for this program. Therefore, a prospective applicant is urged to consult the Table of IC-Specific Information, Requirements and Staff Contacts to determine whether the planned research and training falls within the mission of one of the participating NIH ICs.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Native American tribal organizations (other than Federally recognized tribal governments), and faith-based or community-based organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

The sponsoring institution may be private (profit or nonprofit) or public, including the NIH Intramural Programs and other Federal laboratories.

The applicant institution will be the mentored phase K99 institution. All institution/organization types listed above are eligible for both the mentored and independent phase, with one exception: eligible agencies of the Federal government, such as the NIH intramural program, are eligible only for the mentored phase.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any candidate with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her mentor and organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. Multiple Principal Investigators are not allowed.

By the time of award, the individual must be a citizen or a non-citizen national of the United States or have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status), or for non-U.S. citizen/permanent residents, requirements are described below.

For non-U.S. citizen/permanent residents, the applicant U.S. institution for each phase of the application (K99 or R00) is responsible for determining and documenting in the application that the applicant investigator's visa will allow him or her to remain in this country long enough to (a) transition to an independent research career in the U.S. during the proposed mentored (K99) phase and/or (b) be productive on the research project in the U.S. for the duration of the proposed independent research (R00) phase.

Candidates must have a clinical or research doctorate (including Ph.D., M.D., D.O., D.C., N.D., D.D.S., D.M.D., D.V.M., Sc.D., D.N.S., Pharm.D. or equivalent doctoral degrees) and have no more than 5 years of postdoctoral research training at the time of application (resubmissions must also comply with this requirement). Clinicians (including those with M.D., D.D.S, D.V.M. and other licensed health professionals) in a clinical faculty position that denotes independence in clinical responsibilities but not in research may also be eligible for the K99/R00 award.

Ph.D. (or equivalent research doctorate degree) candidates in positions other than postdoctoral fellow positions: It is recognized that some institutions appoint postdoctoral fellows in positions with other titles although they are still in non-independent training positions. Candidates in such positions are encouraged to obtain confirmation of their eligibility before they begin to prepare their applications. It is incumbent upon the candidate to provide evidence that the position he/she is in complies with the intent of this eligibility requirement.

Evidence for non-independence may include:

  • The candidate's research is entirely funded by other investigator's grants.

  • The candidate's research is conducted entirely in another investigator's assigned space.

  • According to institutional policy, the candidate cannot hire postdoctoral fellows or be the responsible supervisor of graduate students.

  • According to institutional policy, the candidate is not allowed to submit an application as the principal investigator of an NIH research grant application (e.g., R01).

  • The candidate lacks other rights and privileges of faculty, such as attendance at faculty meetings.

  • Conversely, evidence for independence, and therefore lack of eligibility, includes:

  • The candidate has a full-time tenure track assistant professor position (or equivalent).

  • The candidate received a startup package for support of his/her independent research.

  • The candidate has research space dedicated to his/her own research.

  • The candidate may attend faculty meetings, be the responsible supervisor for graduate students, and/or hire postdoctoral fellows.

  • The candidate is eligible to apply for independent research funding as the principal investigator of an NIH R01 or other equivalent research grant.

Clinicians (including those with M.D., D.D.S, D.V.M. and other licensed professionals) in positions not designated as postdoctoral positions: Following clinical training or fellowship training periods, clinicians often obtain a clinical faculty position that denotes independence in clinical responsibilities but not in research. A clinical faculty member who does not hold an independent research faculty position may be eligible for the K99/R00 award, and should contact a Program Director at the relevant NIH Institute for guidance. Clinicians in such positions are encouraged to obtain confirmation of their eligibility before they begin to prepare their applications. Such individuals may also wish to consider other career awards available for junior faculty development.

Individuals are NOT eligible if they:

  • Have currently or previously held an independent research faculty or tenure-track faculty position, or its equivalent, in academia, industry or elsewhere; or

  • Have more than 5 years of related postdoctoral research training at the time of initial application or resubmission(s); or

  • Have been an independent PD/PI on NIH research grants (e.g., R01, R03, R21), NIH career development awards (e.g., K01, K07, K08, K23, K25), or other peer reviewed NIH or non-NIH research grants over $100,000 direct costs per year, or project leaders on sub-projects of program project (P01) or center (P50) grants.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed. An individual may not have two or more competing NIH career development applications pending review concurrently. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Candidates may submit research project grant (RPG) applications concurrently with the K application. However, any concurrent RPG application may not duplicate the provisions of the career award application. K award recipients are encouraged to obtain funding from NIH or other Federal sources either as a PD/PI on a competing research grant award or cooperative agreement or as project leader on a competing multi-project award as described in NOT-OD-08-065.

At the time of award, the candidate must have a "full-time" appointment at the academic institution that is the applicant institution. Candidates who have VA appointments may not consider part of the VA effort toward satisfying the "full time"• requirement at the applicant institution. Candidates with VA appointments should contact the staff person in the relevant IC prior to preparing an application to discuss their eligibility. Under certain circumstances, an awardee may submit a written request to the awarding component requesting a reduction in minimum required percent effort, which will be considered on a case-by-case basis. Details on this policy are provided in NOT-OD-09-036.

Before submitting the application, the candidate must identify a mentor who will supervise the proposed career development and research experience. The mentor should be an active investigator in the area of the proposed research and be committed both to the career development of the candidate and to the direct supervision of the candidate's research. The mentor must document the availability of sufficient research support and facilities for high-quality research. Candidates are encouraged to identify more than one mentor, i.e., a mentoring team, if this is deemed advantageous for providing expert advice in all aspects of the research career development program. The mentor, or a member of the mentoring team, should have a successful track record of mentoring. In such cases, one individual must be identified as the principal mentor who will coordinate the candidate's research. The candidate must work with the mentor(s) in preparing the application. The mentor(s) should describe the career development plan for the candidate (coordinated with the candidate's research strategy). The mentor and any co-mentors are also expected to provide an assessment of the candidate's qualifications and potential for a research career. The research environment and the availability and quality of needed research facilities and research resources (e.g., equipment, laboratory space, computer time, available research support, etc.) must also be described. The description should include items such as classes, seminars, and opportunities for interaction with other groups and scientists. Training in career skills, e.g. grant-writing and making effective presentations, is strongly encouraged.

The applicant institution must have a strong, well-established record of research and career development activities and faculty qualified to serve as mentors in biomedical, behavioral, or clinical research. The institution must demonstrate a commitment to the development of the candidate as a productive, independent investigator and be willing to allow the protected time needed by the candidate. The candidate, mentor (s), and institution must describe a research career development program that will maximize the use of this environment, including available facilities and resources.

For candidates for K99/R00 awards who are non-U.S. citizens with temporary U.S. visas, the sponsoring institution must include information about their visa status, and an assurance that their visas will allow them to remain in the United States long enough to (a) transition to an independent research career in the U.S. during the proposed mentored (K99) phase and (b) be productive on the research project in the U.S. for the duration of the proposed independent research (R00) phase.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-197.html.

AUTISM CENTERS OF EXCELLENCE: CENTERS (P50): RFA-HD-12-195

Components of Participating Organizations

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Deafness and Other Communication Disorders

National Institute of Environmental Health Sciences

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

Application Receipt Date(s): November 16, 2011

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders with early childhood onset. The prevalence of ASD may be increasing, and ASD is more common than previously thought. These disorders, for which there is presently no cure and only limited treatments, generally have lifelong effects.

The NIH historically has supported a vast array of projects in autism research. Beginning in 1997, the Collaborative Programs of Excellence in Autism (CPEA) focused on research related to the possible causes of autism, including genetic, immunological, and environmental factors. The CPEA program resulted from a congressionally mandated conference on the State of the Science in Autism. The attendees identified gaps in the understanding of autism and articulated directions for future research. Both NICHD and NIDCD sponsored the CPEA program. As a result of the efforts of researchers affiliated with the CPEA, data now exist on the genetics and phenotypic characteristics of the largest group of well-diagnosed persons with autism in the world. After the establishment of the CPEA Centers program, Congress enacted the Children's Health Act of 2000. This legislation mandated the establishment of a new autism research program. In response, the five Institutes of the NIH Autism Coordinating Committee (NIH-ACC; represented by NICHD, NIDCD, NIEHS, NIMH, and NINDS) implemented the STAART (Studies to Advance Autism Research and Treatment) program in 2002. Each of the eight STAART centers contributed to the autism research base in the areas of causes, diagnosis, early detection, prevention, and treatment. Collaborations among the STAART centers included a multi-site psychopharmacological clinical trial. In 2007, consolidation of funding from the CPEA and STAART programs resulted in autism centers and networks called the Autism Centers of Excellence or ACE program. In FY 2007 and 2008, five centers and six networks were funded.

The purpose of this Funding Opportunity Announcement (FOA) is to encourage research grant applications to support research designed to elucidate the etiology, epidemiology, diagnosis, treatment, and optimal means of service delivery in relation to autism spectrum disorders (ASD).

In response to the urgent public health significance of ASD, Congress passed the Combating Autism Act (CAA) of 2006. Through this Act, Congress intends to accelerate the pace, and improve the coordination of scientific discovery in ASD research. The Strategic Plan for ASD Research, a requirement of the CAA, was developed with the input of the scientific community, as well as advocates and advocacy organizations, including parents, providers, and individuals with ASD. The plan consists of short and long term research objectives across a range of topics. This FOA is intended to support the broad research goals of the Strategic Plan for ASD Research (http://iacc.hhs.gov/strategic-plan/2011/index.shtml).

NIH will consider "centers" as well as "networks" in response to the ACE initiative. This FOA solicits applications for ACE Centers supported by the P50 mechanism. A companion FOA (RFA-HD-12-196) solicits applications for ACE Networks supported by the R01 mechanism.

This FOA solicits applications for ACE Centers. Centers bring together expertise, infrastructure and resources focused on major questions about autism. Centers should involve collaborations of basic and clinical scientists optimally suited to address the research questions posed. NIH expects Centers to provide an environment and core resources to bring together biomedical, behavioral, and clinical science investigators to study autism. Collaborations involving more than one institution are strongly encouraged to provide optimal resources and expertise. The Centers should provide investigators with well-characterized patients and control subjects, family information, and other scientific resources that facilitate research projects. Applications for Centers must include a minimum of three but no more than six research projects.

An ACE Center must support major multidisciplinary research programs, consisting of interdependent and interrelated subprojects. Meaningful and committed interactions among the disciplines must be evident. Subprojects may share materials, results, data, patient populations, or methodologies. Results of one subproject may well affect the understanding and interpretation of data from another project and thereby influence the nature of the research performed in one or more of the other subprojects. In addition, each subproject must have goals and objectives that focus on the common unifying theme that interrelates the subprojects.

A companion funding opportunity solicits applications for ACE Networks (RFA-HD-12-196). A network will consist of multiple sites focusing on a specific topic of research for R01 support through this funding opportunity. Each network will submit one R01 application that includes subcontracts to the collaborating sites. An ACE Network application must include one or more collaborative projects that require multiple sites for optimal design and conduct of studies. For example, an interrelated series of clinical trials of pharmacologic, behavioral interventions, or a combination of these, could be an example of the focus of such a network. Another example could be a multi-site epidemiology study of risk factors for ASD. Special populations requiring large numbers of participants for each protocol may also be studied best under a network because of enhanced recruitment and other benefits of multi-site subject accrual.

The highest priority will be given to projects related to gaps identified by the 2011 IACC Strategic Plan. Please indicate, when appropriate, to which short or long term objective or area of opportunity from the 2011 IACC strategic plan your project responds.

An ACE Center must include at least one project related to the identification and evaluation of interventions and/or services research. Such projects may also include pilot projects.

Intervention Projects:

  • Identification of individual characteristics that predict response to behavioral, pharmacological and other treatments.

  • Multi-site clinical trials to identify moderators and effective ingredients (e.g. dose, intensity, mode of delivery, age of onset) of intervention treatments.

  • Innovative and newly developed intervention strategies to improve outcomes in school and community settings throughout the lifespan (e.g., academic functioning, social and adaptive behavior, family functioning, employment), including transitions.

  • Development of efficacious drug treatments that target core symptoms of autism.

  • Assessment and interventions for nonverbal school-aged children with autism.

  • Pilot studies, including exploratory clinical trials, aimed to generate data that inform a decision whether to continue further clinical development of the proposed intervention.

Services Projects:

  • Studies to understand how specific types of services, organizational processes and structures, financing mechanisms and evolving technologies and policies affect access to and delivery of services to people with ASD.

  • Studies that include children, as well as transition-age youth and adults.

  • Studies on adults that include strategies that enable post-secondary education, supported employment, health care and community integration.

  • Other priority areas include, but are not limited to:

  • Identification of risk factors (e.g., viruses, medications, immune dysfunctions, mitochondrial abnormalities, environmental chemicals, genetics) that contribute to the development of autism and their associated developmental windows.

  • Identification of biological signatures for autism and their relevance to prediction of treatment response and outcomes.

  • Assessment of characteristics and evaluation of interventions in understudied populations (e.g. adults, individuals from racial and ethnic minorities) and in those with comorbid conditions (e.g. epilepsy).

  • Studies that improve the understanding of underlying biologic pathways that might lead to treatments for genetic conditions related to autism. NINDS is particularly interested in mechanistic analyses of single gene disorders with autistic features (e.g. Tuberous Sclerosis Complex, Rett syndrome, Fragile X syndrome) that may shed light on pathways that are relevant to autism.

The minimal structural requirements of an ACE Center under this FOA are:

  • Research Project(s) - An ACE Center must include at least one research project related to interventions and/or services research. Other projects may address one of the above priority areas. Such projects may also include pilot projects. Those applying for a Type 2 renewal of an ACE Center are encouraged to form new collaborations with investigators.

  • Administrative Core - An ACE Center must include an Administrative Core that promotes an environment of communication and collaboration between investigators. The Administrative Core will establish a Center Advisory Committee including external scientific and lay members (individuals should not be named in the application).

  • Research Training and Education Core - An ACE Center must include a Research Training and Education Core to provide a training environment for pre-doctoral and post-doctoral investigators and to engage the broader community in educational and research activities. As nationally recognized Centers of Excellence in Autism Spectrum Disorders, the ACE Centers are expected to play leadership roles in training new researchers in the field of ASDs and educating and disseminating research findings to the community. Involvement of junior and established researchers who are new to the field of autism is encouraged. Recruitment of investigators from underrepresented racial and ethnic groups and disadvantaged backgrounds is also encouraged.

The minimal data collection requirements of an ACE Center under this FOA are:

All Center applications must include collection of data using the following forms or a justification of why the forms are not appropriate. Additional modifications to these forms may occur periodically.

  • Medical History Form

  • Family History Form

  • Physical Examination Form

  • Genetic Testing Information Form

  • Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), for use according to their published manuals

  • Vineland Adaptive Behavior Scales, Second Edition

  • An IQ or developmental assessment measure, that includes both nonverbal and verbal components and results in standardized scores for both.

  • The NIH National Database for Autism Research (NDAR) houses research data of all types (genetic, imaging, clinical assessment, etc.) from human subjects involved in ASD studies, and is currently on track to receive data from tens of thousands of such subjects. NDAR's first data release occurred in November 2010, making mostly clinical assessment data from over 10,000 research subjects available to qualified investigators. It is expected that in the next several years, ASD data from more than 90% of new investigations will be available in or through NDAR.

All ACE Centers will be required to contribute data to NDAR. Data sharing is required and NDAR will be involved to facilitate sharing activities. NDAR will function as a data repository for all ACE projects. Central clinical coordination and local data management for data cleaning and entry and bio-statistical consulting will be the responsibility of the ACE Center. For more information on NDAR, please visit http://ndar.nih.gov/ndarpublicweb/.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Foreign institutions may not serve as the applicant organization. However, they may participate as part of a consortium. For example, a subproject within an ACE Center may be located at a foreign institution and supported through a subcontract. Funding requests for foreign subcontracts must be made in U.S. dollars. Facilities and administrative costs on foreign consortia will be awarded at 8 percent of the total direct costs less equipment.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

Only one individual may serve as the Center Director. Multiple Center Directors are not permitted. The Center Director must commit a minimum effort of 2.4 person-months per year overall to the Center.

Leaders of individual projects must commit a total minimum effort of 1.8 person-months per year to each project. Multiple project leaders are allowed for individual research projects. If there are multiple project leaders on a project, the combined efforts of the identified project leaders must total at least 1.8 person-months per year.

Multiple Core Leaders are allowed for cores.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Each principal investigator may submit only one application for either an ACE Center or an ACE Network. This does not exclude multiple applications from a single institution, provided each application is submitted by a different principal investigator. No more than two awards will be made at each institution.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-12-195.html.

AUTISM CENTERS OF EXCELLENCE: NETWORKS (R01): RFA-HD-12-196

Components of Participating Organizations

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute on Deafness and Other Communication Disorders

National Institute of Environmental Health Sciences

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

Application Receipt Date(s): November 16, 2011

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders with early childhood onset. The prevalence of ASD may be increasing, and ASD is more common than previously thought. These disorders, for which there is presently no cure and only limited treatments, generally have lifelong effects.

The NIH historically has supported a vast array of projects in autism research. Beginning in 1997, the Collaborative Programs of Excellence in Autism (CPEA) focused on research related to the possible causes of autism, including genetic, immunological, and environmental factors. The CPEA program resulted from a congressionally mandated conference on the State of the Science in Autism. The attendees identified gaps in the understanding of autism and articulated directions for future research. Both NICHD and NIDCD sponsored the CPEA program. As a result of the efforts of researchers affiliated with the CPEA, data now exist on the genetics and phenotypic characteristics of the largest group of well-diagnosed persons with autism in the world. After the establishment of the CPEA Centers program, Congress enacted the Children's Health Act of 2000. This legislation mandated the establishment of a new autism research program. In response, the five Institutes of the NIH Autism Coordinating Committee (NIH-ACC; represented by NICHD, NIDCD, NIEHS, NIMH, and NINDS) implemented the STAART (Studies to Advance Autism Research and Treatment) program in 2002. Each of the eight STAART centers contributed to the autism research base in the areas of causes, diagnosis, early detection, prevention, and treatment. Collaborations among the STAART centers included a multi-site psychopharmacological clinical trial. In 2007, consolidation of funding from the CPEA and STAART programs resulted in autism centers and networks called the Autism Centers of Excellence or ACE program. In FY 2007 and 2008, five centers and six networks were funded.

The purpose of this Funding Opportunity Announcement (FOA) is to encourage research grant applications to support research designed to elucidate the etiology, epidemiology, diagnosis, treatment, and optimal means of service delivery in relation to autism spectrum disorders (ASD).

In response to the urgent public health significance of ASD, Congress passed the Combating Autism Act (CAA) of 2006. Through this Act, Congress intends to accelerate the pace, and improve the coordination of scientific discovery in ASD research. The Strategic Plan for ASD Research, a requirement of the CAA, was developed with the input of the scientific community, as well as advocates and advocacy organizations, including parents, providers, and individuals with ASD. The plan consists of short and long term research objectives across a range of topics. This FOA is intended to support the broad research goals of the Strategic Plan for ASD Research (http://iacc.hhs.gov/strategic-plan/2011/index.shtml).

NIH will consider "centers"• as well as "networks"• in response to the ACE initiative. This funding opportunity solicits applications for ACE Networks supported by the R01 mechanism. A companion FOA (RFA-HD-12-195) solicits applications for ACE Centers supported by the P50 mechanism.

This funding opportunity solicits applications for ACE Networks. A network will consist of multiple sites focusing on a specific topic of research for R01 support through this funding opportunity. Each network will submit one R01 application that includes subawards to the collaborating sites. An ACE Network application must require multiple sites for optimal design and conduct of the study. For example, an interrelated series of clinical trials of pharmacologic, behavioral interventions, or a combination of these, could be the focus of such a network. Another example could be a multi-site epidemiology study of risk factors for ASD. Special populations requiring large numbers of participants for each protocol may also be studied best under a network because of enhanced recruitment and other benefits of multi-site subject accrual.

A companion FOA solicits applications for ACE Centers (RFA-HD-12-195). Centers bring together expertise, infrastructure and resources focused on major questions about autism. Centers should involve collaborations of basic and clinical scientists optimally suited to address the research questions posed. NIH expects Centers to provide an environment and core resources to bring together biomedical, behavioral, and clinical science investigators to study autism. Collaborations involving more than one institution are strongly encouraged to provide optimal resources and expertise. The Centers should provide investigators with well-characterized patients and control subjects, family information, and other scientific resources that facilitate research projects. Applications for Centers must include a minimum of three but no more than six research projects.

An ACE Center must support major multidisciplinary research programs, consisting of interdependent and interrelated subprojects. Meaningful and committed interactions among the disciplines must be evident. Subprojects may share materials, results, data, patient populations, or methodologies. Results of one subproject may well affect the understanding and interpretation of data from another project and thereby influence the nature of the research performed in one or more of the other subprojects. In addition, each subproject must have goals and objectives that focus on the common unifying theme that interrelates the subprojects.

The highest priority will be given to projects related to gaps identified by the IACC 2011 Strategic Plan. Please indicate, when appropriate, to which short or long term objective or area of opportunity from the IACC strategic plan your project responds. At least one of the following priorities must be addressed:

Intervention and evaluation of interventions and services for ASD:

Intervention Projects:

  • Identification of individual characteristics that predict response to behavioral, pharmacological and other treatments.

  • Multi-site clinical trials to identify moderators and effective ingredients (e.g. dose, intensity, mode of delivery, age of onset) of intervention treatments.

  • Innovative and newly developed intervention strategies to improve outcomes in school and community settings throughout the lifespan (e.g., academic functioning, social and adaptive behavior, family functioning, employment), including transitions.

  • Development of efficacious drug treatments that target core symptoms of autism.

  • Assessment and interventions for nonverbal school-aged children with autism.

  • Pilot studies, including exploratory clinical trials, aimed to generate data that inform a decision whether to continue further clinical development of the proposed intervention.

Services Projects:

  • Studies to understand how specific types of services, organizational processes and structures, financing mechanisms and evolving technologies and policies affect access to and delivery of services to people with ASD.

  • Studies that include children, as well as transition-age youth and adults.

  • Studies on adults that include strategies that enable post-secondary education, supported employment, health care and community integration.

  • Other priorities include but are not limited to:

  • Identification of risk factors (e.g., viruses, medications, immune dysfunctions, mitochondrial abnormalities, environmental chemicals, genetics) that contribute to the development of autism and their associated developmental windows.

  • Identification of biological signatures for autism and their relevance to prediction of treatment response and outcomes.

  • Assessment of characteristics and evaluation of interventions in understudied populations (e.g. adults, individuals from racial and ethnic minorities) and in those with comorbid conditions (e.g. epilepsy).

  • Studies that improve the understanding of underlying biologic pathways that might lead to treatments for genetic conditions related to autism. NINDS is particularly interested in mechanistic analyses of single gene disorders with autistic features (e.g. Tuberous Sclerosis Complex, Rett syndrome, Fragile X syndrome) that may shed light on pathways that are relevant to autism.

The minimal structural requirements of an ACE Network under this FOA are:

  • Research Project(s) - Each network will submit one R01 application that includes subawards to the collaborating sites. An ACE Network application must require multiple sites for optimal design and conduct of the study. The research project must address one of the above priority areas. Those applying for a renewal of an ACE Network are encouraged to form new collaborations with investigators.

  • Data Coordinating Center - Applications must have a clearly defined Data Coordinating Center (DCC) section in the research plan that describes the DCC's functions in detail and explains how it will operate independently from data collection sites. Applicants must provide evidence that the data collection sites and DCC are functionally separate, with separate chains of command.

  • Research Training and Education - ACE Networks must provide a training environment for pre-doctoral and post-doctoral investigators and engage the broader community in educational and research activities. The ACE Networks are expected to play leadership roles in training new researchers in the field of Autism Spectrum Disorders and in educating and disseminating research findings to the community. Involvement of junior and established researchers who are new to the field of autism is encouraged. Recruitment of investigators from underrepresented racial and ethnic groups and disadvantaged backgrounds is also encouraged.

The minimal data collection requirements of an ACE Network under this FOA are:

Network applications must include collection of data using the following forms or a justification of why the forms are not appropriate. Additional modifications to these forms may occur periodically.

  • Medical History Form

  • Family History Form

  • Physical Examination Form

  • Genetic Testing Information Form

  • Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), for use according to their published manuals

  • Vineland Adaptive Behavior Scales, Second Edition

  • An IQ or developmental assessment measure that includes both nonverbal and verbal components and results in standardized scores for both

  • The NIH National Database for Autism Research (NDAR) houses research data of all types (genetic, imaging, clinical assessment, etc.) from human subjects involved in ASD studies, and is currently on track to receive data from tens of thousands of such subjects. NDAR's first data release occurred in November 2010, making mostly clinical assessment data from over 10,000 research subjects available to qualified investigators. It is expected that in the next several years, ASD data from more than 90% of new investigations will be available in or through NDAR.

All ACE Networks will be required to contribute data to NDAR. Data sharing is required and NDAR will be involved to facilitate sharing activities. NDAR will function as a data repository for all ACE projects. Central clinical coordination and local data management for data cleaning and entry and bio-statistical consulting will be the responsibility of the ACE Network. For more information on NDAR, please visit http://ndar.nih.gov/ndarpublicweb/.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Foreign institutions may not serve as the applicant organization. However, they may participate as part of the network consortium. For example, a site within an ACE Network may be located at a foreign institution and supported through a subaward. Funding requests for foreign subawards must be made in U.S. dollars. Facilities and administrative costs on foreign consortia will be awarded at 8 percent of the total direct costs less equipment.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Each PD/PI may submit only one application for either an ACE Center or an ACE Network. This does not exclude multiple applications from a single institution, provided each application is submitted by a different principal investigator.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-12-196.html.

SUPPORT OF NIGMS PROGRAM PROJECT GRANTS (P01): PAR-11-220

Components of Participating Organizations

National Institute of General Medical Sciences

Application Receipt/Submission Date(s): September 07, 2014

This funding opportunity announcement (FOA) issued by the National Institute of General Medical Sciences encourages innovative, interactive program project grant applications from institutions/organizations that propose to conduct research which aims to solve a significant biological problem, important for the mission of NIGMS, through a collaborative approach involving outstanding scientists who might not otherwise collaborate. NIGMS supports research in the broad areas of Cell Biology and Biophysics; Genetics and Developmental Biology; Pharmacology, Physiology, and Biological Chemistry; and Bioinformatics and Computational Biology. The program project mechanism is designed to support research in which the funding of several interdependent projects offers significant scientific advantages over support of these same projects as individual regular research grants. Program project grants are investigator initiated, but are restricted to areas of special interest to the individual divisions within NIGMS (see http://www.nigms.nih.gov/About/overview for scientific areas of interests).

Successful program projects generally bring together scientists to apply complementary approaches to work on an important well-defined problem. In addition to individual research projects, applicants may propose one or more shared resource cores if needed for the proposed research. Each shared resource core must provide support and enhance the productivity, cost-effectiveness, and/or research outcome of at least two of the proposed research projects. New cores may be proposed and/or existing cores may be augmented to support the proposed research. In this way the program project can facilitate the support of essential shared core facilities, e.g., major equipment, although the need of a group of investigators for a major piece of equipment or a core facility does not in itself justify a program project grant. Administrative cores, except in special, well-justified circumstances, will not be allowed. It is expected that successful program projects will establish effective collaborations, particularly in emerging areas of research that extend beyond the life of the program project grant itself. Hence, a program project generally has a finite lifetime.

Normally, a program project consists of three to five individual, interdependent projects from different investigators. All of the projects must be relevant to the common unifying central theme, focus, and overall objective of the entire program project. Each individual project should reflect a distinct, separate, scientifically meritorious research effort led by an independent investigator. The individual projects must be clearly interrelated and synergistic so that the research ideas, efforts, and outcomes of the program as a whole will offer a distinct advantage over pursuing the individual projects separately. One PI must be identified as the leader of the program project and that person will be responsible for coordinating the entire program project. The scientist designated as the program project leader bears responsibility for the overall scientific leadership and fiscal management of the program project grant. Each of the collaborating scientists responsible for the individual projects will be independent investigators. The option to designate one of the leaders of the individual projects or cores as project leader of the overall application is allowed. In addition, the program project and each individual project must represent a significant effort on the part of the participating scientists and be distinct from their other funded efforts.

If individuals have substantial support in areas closely related to the program project, their support should be folded into the program project. If their support cannot be folded in, they may participate as associate members. Associate members have full use of, for example, core facilities and contribute to the overall collegiality of the project, but they derive no financial support from it. Participation by associate members may not be used in the justification for a core or a piece of equipment.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply. However, such institutions may participate as members of consortia or subcontractors on the application. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Common Fund/Roadmap text, Collaborative Research, or Projects Greater than 5 years Duration: See instructional documents in the NIH Guide Publishing System for the text to insert.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

Only one program PD/PI is allowed for the overall P01, and only one leader is allowed for each individual project. Multiple PDs/PIs are not allowed in this FOA.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the PHS398 Application Guide.

Current NIH policy permits a component research project of a multi-project grant application to be concurrently submitted as a traditional individual research project (R01) application. If, following review, both the multi-project application and the R01 application are found to be in the fundable range, the investigator must relinquish the R01 and will not have the option to withdraw from the multi-project grant. This is an NIH policy intended to preserve the scientific integrity of a multi-project grant, which may be seriously compromised if a strong component project(s) is removed from the program. Investigators wishing to participate in a multi- project grant must be aware of this policy before making a commitment to the Principal Investigator and awarding institution.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-220.html.

COLLABORATIVE INTERDISCIPLINARY TEAM SCIENCE IN NIDDK RESEARCH AREAS (R24): (PAR-11-221)

Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases

Application Receipt/Submission Date(s): November 15, 2011, November 15, 2012, and November 15, 2013

The complexity of biomedical science often requires the input and expertise of multiple collaborating investigators working as an investigative team. Currently, support for collaborative research may take the form of a large R01 with a Program Director/Principal Investigator (PD/PI) and one or more key personnel and/or collaborators; a multi-PD/PI R01 where credit and responsibility for a project are shared; a Program Project grant (P01) with 3 or more individual and independent projects, with cores, centered on a common theme; or a Center supporting a focused set of resource-related activities. While the R01, P01 and Centers mechanisms can foster certain kinds of collaborations, their structures cannot always readily accommodate interdisciplinary team science that synergizes around a single, critically important research challenge; for example, an unanswered, critical question or construction of a unique resource. In recognition of the need to provide a flexible mechanism to support interdisciplinary team science, the current initiative will support a Collaborative Interdisciplinary Research Program designed to provide flexible support for research teams focused on innovative approaches to a single research challenge relevant to understanding biology that falls within the research mission of the NIDDK. This includes, for example, research related to diabetes, endocrine and metabolic diseases, digestive diseases and nutrition, and kidney, urologic and hematologic diseases and the development of new approaches to prevent, treat and cure these diseases. Collaborative interdisciplinary teams could support basic, or integrated basic and clinical studies that have a potential to move forward the NIH agenda on translation.

The Collaborative Interdisciplinary Research program is designed to support: (a) A team of independent investigators with complementary expertise that will develop a synergistic approach to investigate a single, critically important research challenge; (b) Research projects of high scientific quality supported by strong preliminary data; and that might include the development or use of unique resources.

Investigators, who are considering pursuing a collaborative approach to their research problem, are strongly encouraged to contact NIDDK program staff prior to the projected receipt date to discuss a potential application. The discussion could include relevance of the topic to the NIDDK mission, the scope and approach of the project, and the choice of funding mechanism.

Funding decisions will be based on criteria for programmatic relevance and scientific quality. Successful research should have a major impact on areas relevant to the mission of NIDDK. A description of NIDDK scientific program areas can be found at http://www2.niddk.nih.gov/Funding/default.htm.

Teams that are at a formative stage and are addressing studies in the research areas of Kidney, Urology and Hematologic Diseases (KUH) have the opportunity to submit a "Seeding R24". For details of this mechanism, follow this link to the KUH webpage (http://www2.niddk.nih.gov/KUH/KUHHome/default.htm).

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign organizations) are eligible to be represented by members of a collaborative team but may not apply for funding under this FOA. Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

The R24 is a flexible "R"• type grant mechanism that can be used to encourage a multi-disciplinary, team based approach to complex challenges in biomedical science in ways that are not often the case with the traditional R01. The PD/PI will submit the R24 from his/her institution (hereby termed applicant institution). Other members of the team may serve as co-investigators; or as a group of multiple-PDs/PIs. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide. Funding to PDs/PIs at institutions other than the applicant institution will be administered according to the guidelines of a consortium. The Program Director/Principal Investigator of an R24 grant may be located at one institution while other members of the collaborative team may be located at the same, affiliated, or other institutions. Members of the team need not have interacted previously on this, or other problems.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the PHS398 Application Guide and must include an introduction addressing the previous peer review critique from the Summary Statement.

Applicants may submit Renewal applications for up to a total of 10 years of support. Institutions may submit more than one application. Individual PDs/PIs may submit one application.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-221.html.

VIRTUAL REALITY TECHNOLOGIES FOR RESEARCH AND EDUCATION IN OBESITY AND DIABETES (R01): PA-11-211

Also note: Virtual Reality Technologies for Research and Education in Obesity and Diabetes (R21): PA-11-212

Details at: http://grants.nih.gov/grants/guide/pa-files/PA-11-212.html

Components of Participating Organizations

National Heart, Lung, and Blood Institute

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Office of Behavioral and Social Science Research

Telemedicine and Advanced Technology Research Center

Application Receipt/Submission Date(s): Multiple dates, see announcement

The public health infrastructure is being overwhelmed by problems related to over-eating and under-exercising, and it has become clear that many, perhaps most, people have difficulty assimilating and implementing information on optimal diet and physical activity. Furthermore, the emotional, cognitive, and logistical complexities of diabetes management have resulted in a situation where a large fraction of patients are in sub-optimal glycemic control, leading to poor clinical outcomes and high expenses. Even if individuals are willing to adhere to professional and public health guidance, it is hard to navigate the emotional demands, environmental choices and opportunity cost issues that present themselves at the point of decision. This is the cause of failure for many approaches seeking to promote positive behavioral changes, which is of particular concern for individuals with obesity and diabetes.

Virtual Reality (VR) technologies might prove useful in bridging the gap between information (healthy population guidance or therapeutic lifestyle change guidance for obesity and diabetes) and sustainable behavior change. VR technology allows users to interact with (rather than simply observe) computer-simulated environments, typically with adapted flat-screen monitor displays or stereoscopic goggles, but also sometimes with tactile ("haptic") or other sensory feedbacks including taste and smell. Online communities and virtual worlds with avatars (animated characters representing oneself or others) are increasingly a component of the everyday social world for many people.

VR applications are currently in development and use for a number of health- and medicine-related issues, notably rehabilitation medicine (stroke, Parkinson's disease, pain control in burn victims), behavioral medicine (phobias, post-traumatic stress disorder, drug addiction, autism), and surgery (technical training, robotics, remote site treatment). However, except for small studies in clinical eating disorders (anorexia, binge eating), there has been almost no development of the field in relation to common issues of food intake, food choice and encouragement of physical activity among the broader population.

VR technology could be used to complement motivational interviewing, assess emotional states of readiness for behavioral change, and help patients to grapple with their emotional reactions to food choices. The visual presentations could assist patients in adjusting their distorted assessments of portion sizes; correcting their unrealistic expectations of the rate of weight loss; managing sensory experiences that occur as a result of behavior change, such as hunger or satiety from altered consumption patterns, or delayed muscle soreness from unaccustomed exercise; and enhancing their sense of self-efficacy by giving them successful experiences in navigating virtual environments.

VR also might be suitable for addressing adherence barriers in cardiovascular exercise rehabilitation (particularly for coronary artery disease, heart failure, and peripheral arterial disease) such as perceived exertion, anxiety, and capacity to walk to a prescribed duration and intensity. Another clinical use of VR might be in the provision of non-judgmental support for patients with various medical conditions through virtual coaches, and it might be especially suitable for housebound or reclusive individuals with social anxieties or mobility restrictions due to morbid obesity or other medical conditions. VR could be used in the therapeutic setting as a component of patient visits, to help guide and select educational materials and strategies and timelines. It might be an especially suitable modality for children, adolescents and young adults, who already are becoming familiar with VR as an entertainment technology. VR could also be applicable to individuals with low verbal or numerical literacy who may be more oriented to pictorial (vs. written or abstract) information.

An evolving body of evidence indicates that poor sleep behaviors and insufficient sleep may be causally linked with disordered endocrine and appetite regulation and with risk of metabolic syndrome, diabetes, hypertension and clinical cardiovascular disease. VR technology presents new opportunities to apply recent advances in sleep research in relation to obesity and diabetes risk by objectively evaluating individual sleep and alertness status, delivering personalized guidance on healthy sleep behaviors, implementing physician-recommended treatments (e.g., positive airway pressure devices, light therapy), and assessing treatment outcomes in terms of changes in sleepiness, psycho-motor vigilance, and ocular markers of sympathetic tone. Sleep parameters (e.g., schedules, phasing, quality and quantity), perceptive and affective aspects of sleepiness (e.g., cognizance of sleepiness, self-monitoring of sleep habits), and sleep deprivation consequences (slower reaction times and impairments in memory, cognition, emotional processing, judgment, and decision-making) are all amenable to study with VR.

VR has some unique characteristics as a research tool. The virtual environments can be designed to address specific hypotheses, and data on the study participant's response to the intervention can be collected in high detail without additional intrusiveness. Phenomena that are amenable to study, and also treatment, include cue responsiveness and extinction through virtual exposure, a feature that has been used to advantage in treatment of phobias and addictions. Visual presentations can be tailored to the user, along with therapeutic guidance to modify affective reactions and choices, and can prepare the user for future "real-world" encounters, thus making VR suitable for role-playing and training. Performance feedback, an essential component of learning and skill acquisition, can occur in real-time; thus VR can be used as a teaching tool and also to study cognitive processing of information presented in increasingly complex ("hierarchical") environments, a research approach that often is not practical in "real world" settings. Also, the capability to distribute identical virtual environments across multiple locations gives new meaning to the concept of multi-site data collection.

For researchers, an advantage is that the VR approach can simultaneously deliver an intervention and collect data on how it is utilized, particularly with regard to the cognitive and emotional processes involved. Study design and methodology challenges include: identification of appropriate control groups and control conditions, and of characteristics of rigorous efficacy and effectiveness studies of VR; exploration of ethical issues with different types of studies such as direct comparison designs (Standard of Care [SOC] vs. VR) and additive designs (SOC vs. SOC+VR); characterization of how participant traits (such as age, literacy and numeracy level, motivation and other cognitive and psychosocial traits), and previous gaming experience moderate technology usability and study outcomes; development of well-defined metrics for assessment of interventions and outcomes, including actual as well as intended VR "dose;" development of VR research tools that could be used in group or multi-site formats (e.g. classrooms); and development of methods for mining data from existing health games for research purposes.

There is a need for both developmental VR research leading to new methods and technologies and marketable commercial products. There is also the need for research that provides a venue for well-powered effectiveness trials of the new interventions. Progress in the field will be enhanced by multidisciplinary collaborations between the technology industry and academia, and among researchers with diverse expertise in biomedical sciences (such as endocrinology, nutrition, and exercise physiology), behavioral science and pedagogical disciplines, and computer sciences including VR technologies. There is a need to document and evaluate currently available off-the-shelf programs. Projects will need to be clearly defined with regard to: research questions, technical approach, VR platforms, target population (by age, health condition, psychological status, education or literacy level, etc), and research outcomes. Many projects can be usefully conducted taking advantage of already existing tools, games, and software, although there is also a need to develop unique technologies.

U.S. Army Medical Research and Materiel Command (USAMRMC)

The Telemedicine and Advanced Technology Research Center (TATRC) has substantial in-house subject matter expertise and experience in the application of information technologies, virtual reality, augmented reality, and gaming technologies for healthcare. If the applicant would like to have the research project considered for supplemental funding from TATRC, a paragraph defining the military relevance should be included as such. Note that NIH grants policies as described in the NIH Grants Policy Statement will apply to all applications submitted and awards made in response to this joint-agency FOA.

Applications should involve development, use or adaptation of immersive or non-immersive VR environments. Those projects focusing only on electronic means of research data collection (so-called "e-tools"), without VR components, will not fit the research objectives of this FOA.

Potential areas for hypothesis-testing research, and for exploratory, developmental or evaluation research, include (but are not limited to):

Using VR to foster desirable eating, physical activity, and other health-related behaviors:

  • Making smarter eating choices in various locations (such as home, restaurants, school cafeteria).

  • Understanding the effects of chemical senses input (taste, smell) in combination with VR modalities on learning and motivation processes related to food intake and food choice.

  • Training for more healthful food purchasing and food use decisions (including shopping lists, budgeting, menu planning and food preparation skills).

  • Counteracting food marketing efforts.

  • Assisting parents in teaching small children better eating habits (e.g. eat at table, eat variety of foods, try new foods, eat fruits and vegetables).

  • Training in portion size effects on weight gain and loss.

  • Retraining conditioned emotional and behavioral responses to food and eating contexts (cue-exposure of unhealthful foods or contexts where unhealthful eating behaviors occur).

  • Assessing reliability and outcomes of existing "health games" or "serious games."

  • Improving self-efficacy by VR-guided practice of desired behaviors, including role-playing, scenario navigation, and presentation of information matched to individual learning style and motivational factors.

  • Evaluating genetic/familial influences on perception of portion size and other visual dimensions of food availability/appearance in relation to food choices, caloric intake, and satiety.

  • Evaluating and modifying sleep patterns and behaviors, especially in relation to diet, physical activity, and other aspects of obesity and diabetes prevention and management.

Using VR to motivate by "fast-forwarding" to the future:

  • Illustrating how changes in physical activity or diet will lead to changes in weight and body size.

  • Using avatars or intelligent agents to show consequences of unhealthful behavior and to model healthful behavior.

  • Understanding characteristics of avatars that modify effectiveness of interventions, including the degree to which they must be sufficiently similar to how user views self.

  • Modifying perception of body image and other aspects of appearance.

  • Modeling effects of changes in community food choice availability and built environments on weight, physical activity, health, and illness.

  • Utilizing social network capabilities of VR:

  • Evaluating impact of social network systems with reward systems (points or credits) for desirable health-related behaviors (buying or eating healthful foods; engaging in regular physical activity; improving sleep habits; improving diabetes self-monitoring).

  • Exploring how social context affects competitive or collaborative activities.

  • Providing and evaluating family interventions.

  • Evaluating usefulness of VR for social support for diabetes.

Utilizing motivational and teaching aspects of VR technology:

  • Embedding obesity and diabetes education and motivation in existing VR games and systems.

  • Using VR to make behavior change more reinforcing and participatory.

  • Monitoring behavior and providing individualized feedback, including rewards and goal-setting.

  • Understanding the cognitive processes involved in learning and applying health- and nutrition-related information.

  • Understanding the short-term vs. long-term motivational aspects of VR, including attenuation of novelty, and how this influences effectiveness and adherence.

  • Understanding determinants of decision processes involved with acceptance, adoption, maintenance, and other aspects of good vs. poor adherence to prevention and treatment regimens for obesity and diabetes.

  • Understanding the role of external visual cues in providing reinforcement and motivation for exercise and increased daily physical activity in sedentary patients with diabetes or obesity or in patients needing cardiovascular exercise rehabilitation.

  • Understanding components of cue responsiveness in diabetes and obesity management skills under environmental conditions of increasing complexity.

  • Understanding cognitive processing of written vs. visual presentations of health and nutrition information in obese or diabetic patients with low print or numerical literacy skills.

Using VR to extend the availability and capacity of health care providers:

  • Establishing extended classrooms for diabetes education.

  • Providing less threatening and more accessible behavioral coaching for children.

  • Enhancing displays and presentations of patient data for review by health care providers.

  • Providing clinician training in how to counsel subjects on weight management.

  • Providing training to clinicians and other health care professionals (dietitians, clinical exercise physiologists) in health behavior-related referral for obese or diabetic patients.

  • Techniques for patient counseling.

  • Modification of bias in the clinical interaction setting (such as negative views towards obese patients).

  • Enhanced displays and presentations of patient data for review by health care providers.

  • Less threatening, more accessible behavioral coaching for patients of various ages.

Social networking capabilities of VR, including:

  • Social support through online communities for conditions such as obesity (particularly morbid obesity), post-bariatric surgery status, diabetes in children and adults, and extreme de-conditioning through inactivity.

  • Impact of social network systems with reward systems (points or credits) for desirable health-related behaviors (buying or eating healthful foods; engaging in physical activity; improving sleep habits; improving diabetes self-monitoring).

  • Effects of social context on competitive or collaborative activities.

  • As a modality for individual and family interventions in various research, preventive, and therapeutic settings (home, school, clinic).

  • Motivational, learning, affective, and perceptual aspects of VR technology, including:

  • Optimal characteristics for obesity and diabetes education as embedded in existing VR games and systems.

  • Optimal characteristics for obesity and diabetes education as embedded in existing VR games and systems.

  • Efficacy, reliability, and outcomes of game orientation ("serious games") to make behavior change more enjoyable and participatory.

  • Monitoring behavior and providing individualized feedback, including rewards and goal-setting.

  • Components of cue responsiveness in diabetes and obesity management skills under environmental conditions of increasing complexity. Understanding the short-term vs. long-term motivational and decision-making aspects of VR, including attenuation of novelty, and how this influences treatment effectiveness as well as acceptance, adoption, maintenance, and other aspects of good vs. poor adherence to prevention and treatment regimens.

  • Cognitive processes involved in learning and use of health- and nutrition-related information, especially in obese or diabetic patients with low print or numerical literacy skills.

  • Genetic and/or familial influences on perception of portion size and other visual dimensions of food availability/appearance in relation to food choices, caloric intake, and satiety.

  • Pain distraction, motivation enhancement, and balance training using immersive visual environments, "haptic" systems (i.e., simulated tactile feedback based on pressure, touch, and vibration sensors), and other VR modalities in supervised rehabilitation exercise therapy for cardiovascular diseases and diabetes complications such as coronary heart disease, peripheral neuropathy, stroke, and peripheral arterial disease.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-211.html.

CLINICAL TRIAL PLANNING GRANTS IN TYPE 1 DIABETES (R34): RFA-DK-11-010

Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases

National Heart, Lung, and Blood Institute

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Institute of Neurological Disorders and Stroke

Application Receipt Date(s): March 15, 2012

Type 1 diabetes is a serious chronic illness. New types of insulin, along with improved management and monitoring technologies, have the potential to improve outcomes. However, diabetes management requires complex balancing of medication dosing, diet and exercise in order to achieve good glucose control while avoiding hypoglycemia. Achievement of good glucose control is also dependent on frequent self-monitoring of blood glucose values. The constant burden of the disease affects the quality of life of individuals with type 1 diabetes and their families, and may be associated with poor adherence to medical regimens.

The results of the Diabetes Control and Complications Trial and its long-term follow-up through the Epidemiology of Diabetes Interventions and Complications study clearly demonstrate the efficacy of good glucose control in preventing the long-term vascular complications of diabetes. Nevertheless, despite efforts of patients to keep their glucose levels as normal as possible, it is still nearly impossible for individuals with type 1 diabetes to achieve the precise level of glucose control attained by a healthy pancreas. Therefore, individuals with type 1 diabetes inevitably experience both hypo- and hyperglycemia; the latter may result in organ damage that produces morbidity for the individual and contributes to the high cost of health care for society. In the United States, diabetes is the leading cause of new cases of blindness in working age adults, non-traumatic lower leg amputations and kidney failure. No organ system is immune from the microvascular damage caused by hyperglycemia. Heart disease is increased by up to ten-fold in people with type 1 diabetes compared to the general age-matched population. In addition, individuals with diabetes have a life span that is reduced by up to 15 years.

Therefore, NIH wishes to test interventions to improve clinical management of type 1 diabetes across the lifespan. These trials should be designed to improve glycemic control and/or treat or reduce diabetes complications. If successful, the results of such trials should be of practical importance to clinical management and applicable immediately.

This FOA will utilize the NIH Clinical Trial Planning Grant (R34) to support the development of clinical trials in individuals with type 1 diabetes. Contingent on the merit of the proposed trials and the availability of funds, NIH anticipates funding of up to three full scale trials from the funded R34 planning grants. During the early funding period of the R34 grant, the investigators will have the opportunity to revise the protocol based on considerations raised in peer review. NIH will then seek external input that will guide priorities for the support of a limited number of full clinical trials selected from the funded R34 protocols. Those clinical trials will be conducted in collaboration with a single data coordinating center that will be awarded through a future FOA. The data coordinating center will work with R34 awardees to finalize the protocol and budget, complete administrative tasks and recruit clinical sites. The data coordinating center award will provide support for the conduct of the selected trials. Clinical trials developed under R34 grants that are not prioritized for implementation through this data coordinating center may be appropriate for support through other funding sources or mechanisms.

NIH intends to promote clinical research to improve the treatment of individuals with type 1 diabetes. To accomplish this goal, this FOA uses the NIH Clinical Trial Planning Grant (R34; http://grants.nih.gov/grants/funding/r34.htm) to support the development of clinical trials with the characteristics described below. The R34 Planning Grant is intended to support all administrative study group activities that are required in order to begin recruitment of subjects. These activities include, but are not limited to: establishing the research team, developing tools for data management and oversight of the research, defining recruitment strategies, finalizing the protocol, writing the Manual of Operations, establishing a data and safety monitoring plan, and initiating the IRB approval process. The R34 Planning Grant application should include a fully developed trial protocol and trial budget. The R34 Planning Grant is not for the collection of preliminary data or the conduct of pilot studies to support the rationale for a clinical trial.

The application should include a rationale for the future clinical trial, documenting significance and need, and describe the potential impact of the clinical trial on health care and practice. Preliminary results and background to support the trial should be provided. The application should include the trial design, including a description of the study population with inclusion and exclusion criteria, a detailed power calculation, and outcomes measures. If surrogate end-points are proposed, a justification for their use should be included. The availability of the requisite patient population and plans for recruitment and retention should be described. Issues and challenges related to adherence to the proposed intervention should be addressed. The application should include a budget for the full trial. Finally, the application should describe the activities proposed to be conducted during the funding period.

A successful R34 will have the potential to lead to a clinical trial that meets the following criteria:

  • If successful, the results of the future trial should be readily applicable to clinical practice. The intervention should already be approved for use in patients or be in clinical practice. The purpose of this initiative is not to validate new technologies, test new therapeutics or elucidate pathophysiologic mechanisms.

  • The future clinical trial should be supported by strong preliminary data that justifies pursuing the trial.

  • The future trial must have a well-defined and clinically important outcome. Trials for improving the management of type 1 diabetes must include a clinical diabetes measure (e.g., improved HbA1C, or decreased diabetic ketoacidosis or hypoglycemia). Trials for the prevention or treatment of diabetes complications must include as an outcome measure either a clinical end-point or a well-validated surrogate marker. The choice of outcome measure should be justified and supported in the application.

  • A target population of patients with type 1 diabetes is required. The trials may include patients across the life-span, or, if scientifically justified, may focus on a specific age group (e.g., infants, adolescents, pregnant women or the elderly). Given the similarities of microvascular complications between type 1 and type 2 diabetes, clinical trials in this area could include patients with type 2 diabetes, if required for sample size. However, since macrovascular disease may have a different pathophysiology in type 1 and type 2 diabetes, studies of macrovascular disease should be restricted to individuals with type 1 diabetes. Applications should discuss the plans for recruitment and feasibility of meeting recruitment goals. The intent of this initiative is to improve the management and treatment of individuals with type 1 diabetes in the United States. Therefore, interventions that are environmentally or culturally specific or deal with specific health care systems must be conducted in the United States.

  • The initiative addresses a broad range of research topics in the area of type 1 diabetes management and complication prevention and treatment. Exceptions are trials related to immune modulation, islet transplantation, retinopathy and the "artificial pancreas," as efforts in these areas are currently underway and may be expanded through other mechanisms.

Appropriate topics as a focus for a clinical trial include, but are not limited to:

Studies to promote adherence: The proposed clinical trials may be aimed at developing and refining innovative strategies to improve adherence to medications and medical regimens. Intervention content and/or delivery methods should be informed by the existing body of clinical and behavioral research, as well as new or emerging basic behavioral or social science findings. Interventions may be targeted to any group across the lifespan, but interventions for adolescents or emerging young adults are of particular interest. Interventions may be targeted to the individual, family, social network, health provider, health system or any combination. The primary outcome for adherence studies must be a measure of glycemia (e.g., improved HbA1c, or decreased diabetic ketoacidosis or hypoglycemia). For adherence studies related to complications, the primary outcome must be an actual disease end-point or an established surrogate marker. Secondary outcomes should include a measure of adherence to the target behavior(s). Measurement of psychosocial outcomes is encouraged. Research to improve adherence may focus on issues such as improving health literacy and/or numeracy; addressing health beliefs that may interfere with adherence; improving social or family support systems; enhancing uptake of technologies shown to be associated with improved glycemic control; and improving outcomes by addressing structure and communication of the health care provider team.

Studies to improve glycemic control using existing diabetes management technologies or medications: The immediate goal of diabetes treatment is to maintain glucose values near normal. Individuals with type 1 diabetes must constantly balance the immediate danger of hypoglycemia with the long-term risk of developing complications due to hyperglycemia. There is a need for better medical regimens and tools to limit glycemic variability and to help patients achieve and sustain tight glucose control without developing hypoglycemia, which can be debilitating and life-threatening. While the development of new pharmacologic agents and new devices (improved continuous glucose monitoring systems and a closed loop or artificial pancreas) is highly desirable, such work is outside the scope of this FOA. Studies submitted under this FOA must use currently available techniques and tools for proposed interventions. Any therapeutic agents or devices used must be FDA-approved. For example, studies may use approved insulin pumps or continuous glucose monitoring to improve glycemic control but may not propose to develop or use non-FDA approved devices to "close the loop." Studies directed at decreasing the prevalence of hypoglycemia and diabetic ketoacidosis are encouraged. Research to improve use of existing therapeutics and diabetes management technologies might include testing specific medical regimens, evaluating management approaches that involve the medical team and/or communication between the medical team and the individuals with diabetes, targeting lifestyle needs, or managing barriers to optimal care.

Studies to treat or reduce complications: Until type 1 diabetes can be prevented or cured, intensive research is needed to prevent and treat the micro- and macrovascular complications of diabetes. Applications may propose future trials to test interventions that improve glycemic control (see above), or address other risk factors associated with the development of complications (e.g., hypertension, dyslipidemia, and pro-inflammatory and coagulation pathways). Future clinical trials can focus on systemic or specific complications, including myocardial infarction, cardiomyopathy, heart failure, stroke, peripheral arterial disease, congenital cardiovascular malformations in offspring of mothers with T1D, sudden death in adults and children related to cardiac autonomic neuropathy, coagulopathies, altered clotting propensity, thrombotic abnormalities, cognitive impairment, depression, wound healing, peripheral sensory neuropathy, autonomic neuropathy, nephropathy, erectile dysfunction, gastroparesis, bladder dysfunction or hypoglycemia unawareness. Applications can also focus on sleep health issues for children with T1D and their parents, especially in relation to the management of nocturnal hypoglycemia, and subsequent impact on memory consolidation, learning and school performance, as well as on parental stress. The outcome measure should be either an actual disease end-point or an established surrogate marker. Studies to develop and/or validate new or emerging biomarkers are outside the scope of this FOA.

Studies to inform the management of type 1 diabetes in subpopulations: If scientifically justified, future trials may focus on a specific age group (e.g., young children, adolescents or the elderly) in order to address management issues unique to the group, including the development of appropriate HbA1c targets. Proposed trials may also test interventions to improve outcomes in individuals at different stages of morbidity (e.g., optimizing glycemic control in the dialysis patient). Studies to optimize pre-conception and pregnancy care of women with type 1 diabetes to improve outcome in both mothers and offspring are also of interest.

In the event of an award, the NIDDK and the Principal Investigator will agree on a list of milestones to be completed during the R34 project period. Prospective applicants should note that funding of an R34 does not guarantee or imply funding for the future clinical trial.

Applicants are encouraged to contact NIH staff to discuss the applications process.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving Institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-11-010.html.

CLINICAL TRIALS DEVELOPMENT RESOURCE FOR HEMATOLOGIC DISORDERS (U24): RFA-HL-12-016

Components of Participating Organizations

National Heart, Lung, and Blood Institute

Application Receipt Date(s): October 13, 2011

The objective of this FOA is to provide critical and necessary support in the development of feasible and well-designed multicenter clinical trials focused on hematologic disorders. The Clinical Trials Development Resource will provide clinical trial methodology expertise to assist grantees of the Clinical Trials Planning Program for Rare Hemostatic and Thrombotic Disorders (U34) (RFA-HL-12-023) and the NHLBI Clinical Trial Pilot Studies (R34) (PAR-10-005) awards in the area of blood diseases and resources.

Carefully designed and precisely implemented clinical research is needed to guide health care delivery for individuals with blood disorders or those receiving blood-based products. However, the subject matter experts most aware of the clinical needs may not have the resources necessary to successfully develop, conduct and complete these challenging trials. Expertise is needed to navigate the specific hurdles inherent in the study of patient populations with rare hematologic disorders or to recruit target subject populations that are not under the hematologist's direct clinical care.

Multicenter clinical trials frequently have a 6-12 month delay in start-up and difficulty meeting accrual timelines. Many studies have a substantial unobligated balance during the first 2 years and request a no cost extension to complete subject enrollment and data analysis. Therefore there is a need for expert assistance in the planning, timely initiation and successful completion of investigator- initiated clinical trials.

The successful planning and execution of clinical trials require access to the appropriate resources in clinical trials design and methodology. Although there are existing institutional consultative resources, a recent NCRR/NHLBI evaluation of the availability of resources to the hematology clinical research community indicated that these units may have difficultly providing timely and specialized services within the context of specific institutional objectives and are unable to expand services without additional funding. Therefore, a centralized and specialized Resource, focused on providing clinical trial design, methodology expertise and assistance to the hematology community would be essential, especially at the planning stage.

The Clinical Trials Development Resource for Hematologic Disorders will provide consultative services for the development of multi-site clinical trials to grantees of the Clinical Trials Planning Studies for Rare Thrombotic and Hemostatic Disorders (U34) program and to grantees of the NHLBI Clinical Trial Pilot Studies (R34) (PAR-10-005) program, in the area of blood diseases and resources. The primary objective of this program would be to assist in the development of well-designed and feasible investigator-initiated clinical studies that would be initiated in a timely manner and successfully completed.

The types of services that the U24 Clinical Trials Development Resource for Hematologic Disorders would be expected to offer would include but are not limited to:

  • Assistance in clinical trial design and recruitment strategy, and addressing in particular the special needs for studies in rare diseases and pediatric populations.

  • Biostatistical support.

  • Consultative assistance in developing site and subject recruitment strategies.

  • Guidance on regulatory issues and needed documentation.

  • Bioethics consultation.

  • Consultative assistance in preparing clinical protocol, manual of procedures, training materials, consent forms and data safety monitoring plan.

  • Guidance in planning a multi-site clinical trial, including multiple-site IRB approval, contracting, as well as efficient and cost effective trial management.

  • Assistance on preparation of agreements as necessary for industry collaborations.

  • Assistance in identifying and establishing collaborations with patient advocacy groups, professional societies (e.g. the Society for Clinical Trials) and other organizations that could aid in implementation of the trial.

  • Development of investigator-targeted education in clinical trials methodology as well as approaches for formal and informal U34 investigator interactions.

During the five-year funding period the Resource will need to have the expertise and capacity to provide services for ten U34 Clinical Trials Planning Studies for Rare Thrombotic and Hemostatic Disorders grants and approximately ten R34 NHLBI Clinical Trial Pilot Studies Hematologic Disorder grants. It is anticipated that the U34 grants will be awarded over the first three years of the program. Detailed information on this program can be found in the companion FOA announcement. The U34 grantees will be required to meet with the Resource early in the first year of their award to jointly develop a timeline for the planning activities and identify Resource services that will aid in accomplishing the goals of their clinical trial planning grant. Grantees of the R34 with programs in hematologic disorders will be offered the utilization of resource services during the funding period of their grant. The Resource should have flexible staffing and a well defined process to interact with U34/R34 investigators who are expected to have diverse clinical programs and consultative service needs. The Resource should be able to add the necessary expertise, based on the requirements of the specific U34/R34 needs. The professional expertise should be a priority over the geographical location during a selection of the consultants. In addition, the Resource will organize an annual meeting/workshop for the U34/R34 investigators to provide information on topics of clinical trial development and management. The Resource will also provide a system for monitoring and evaluating the utilization of the consultant services requested by and provided to the investigators.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving Institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-016.html.

CLINICAL TRIALS PLANNING STUDIES FOR RARE THROMBOTIC AND HEMOSTATIC DISORDERS (U34): RFA-HL-12-023

Components of Participating Organizations

National Heart, Lung, and Blood Institute

Application Receipt Date(s): October 13, 2011, October 15, 2012, October 17, 2013

The purpose of this FOA is to provide support specifically for the planning phase of Phase III multicenter investigator-initiated clinical trials focused either on rare hemostatic and thrombotic disorders, or on more common hemostatic and thrombotic disorders that occur rarely in special patient populations (for example: neonates, children, pregnant women). The FOA will support the development of feasible and well-designed clinical trials utilizing consultative services provided by the Clinical Trials Development Resource for Hematologic Disorders (U24) (RFA-HL-12-016).

Rare hemostatic and thrombotic disorders (hereditary and acquired) present unique challenges in diagnosis and treatment. Similar problems exist in special populations, such as children and pregnant women, for whom the applicability of evidence obtained from general population studies may not optimally inform treatment decisions. Consequently, standard of care in such cases is often primarily based on expert opinion, rather than informed by an evidence base. Clinical trials are now necessary to investigate new agents and regimens that: 1) improve and maintain anti-thrombotic efficacy without compromising safety or increasing treatment-related morbidity for rarely occurring thrombotic disorders; and 2) prevent and treat both life-threatening hemorrhage and long term disease-related morbidity associated with rare hereditary and acquired bleeding disorders.

Effective clinical research in rare coagulation disorder populations or in populations rarely affected by more common hemostatic and thrombotic disorders pose unique challenges and require specific expertise in study feasibility and design, subject recruitment strategy and innovative complex statistical and analytical methodology. Furthermore, pilot studies are often precluded. The subject matter experts most aware of the need for clinical research in these areas may not have the resources necessary to successfully develop, conduct, and complete these challenging trials.

For these purposes a planning U34 mechanism is being introduced to support the preparatory phase for investigator-initiated clinical trials. The companion Clinical Trials Developing Resource for Hematologic Disorders (U24) awardee(s) will provide funded U34 investigators with the much needed assistance required to plan these methodologically challenging multicenter studies.

It is expected that receipt of a planning U34 grant will lead to the timely submission of an application for support of the full-scale trial, incorporating the elements developed under the planning grant. This program is designed to: 1) permit early peer review of the rationale for the proposed clinical trial; 2) permit assessment of the design of the proposed trial in its current, early form; 3) provide support for the development of a detailed manual of procedures (MOP); and 4) support the development of other essential elements of a clinical trial, such as:

  • Planning trial infrastructure and finalizing research team(s) and participating clinical sites.

  • Finalizing plans for addressing Federal and NIH gender/minority inclusion and human subjects protection requirements.

  • Establishing collaborative arrangements, including agreements with industry, if needed.

  • Instituting measures to assure standardization of procedures across sites and among staff.

  • Developing necessary tools for data collection and data management.

  • Developing/finalizing safety and monitoring plans according to the NHLBI Policy.

  • Developing plans for training that may be required to carry out the proposed trials.

  • Conducting small-scale pilot trials to verify feasibility and assess accrual strategy.

  • Consulting with FDA for regulatory advice for drugs, biologics or devices that may require an IND or IDE.

The Clinical Trial Planning Grant Program is not designed for the collection of preliminary data or the conduct of pilot studies to support the rationale for a clinical trial. Applicants should consider PAR-10-005: NHLBI Clinical Trial Pilot Studies (R34) as a potential funding mechanism to support pilot or feasibility studies.

The investigators in this program will be required to access the consultative services made available through the Clinical Trials Development Resource for Hematologic Disorders (U24) to jointly develop a timeline for the planning activities and identify the services the Resource will be required to provide. It is expected that this program will allow for early identification of non-feasible trial concepts, and will increase the number of important R01 clinical trials that are successfully completed. If warranted by the activities conducted, U34 awardees may prepare and submit an R01 application to support a full scale trial during the final year of the U34 award period. Prospective applicants should however note that funding of a Clinical Trial Planning Grant does not guarantee or imply funding for a subsequent application.

This FOA is designed to support planning activities in preparation for a full-scale Phase III multicenter clinical trial. These planning activities are primarily logistical, conceptual, and/or technical in nature. They do not involve the collection of data typical of research-related activities supported by the traditional NIH research project grant. As such, the evaluation of U34 applications will focus on the justification of or need for the proposed trial along with the appropriateness of the proposed planning activities.

Applicants are encouraged to contact the NHLBI Scientific Research Contact(s) for this U34 FOA to address questions concerning the U34 application.

Research Examples include but are not limited to:

  • Clinical trials for safe and effective prophylaxis and treatment of thrombosis in neonatal and pediatric populations.

  • Post-licensing optimization of new anticoagulants in patients with inherited thrombophilia.

  • Studies to increase therapeutic options for rare hemostatic disorders.

  • Clinical studies to identify risk factors for antibody development and thrombotic complications for immune-mediated thrombotic disorders.

  • Clinical study to transition young adult hemophilia subjects on primary prophylaxis regimens to an individually tailored (dose/frequency) replacement therapy.

  • Studies on assessment of genetic and environmental risk factors for inhibitor formation to inform the best therapeutic options for inhibitor eradication in both pediatric and the adult hemophilia population.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving Institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-023.html.

CONTRACEPTIVE DEVELOPMENT RESEARCH CENTERS PROGRAM (U54): RFA-HD-12-185

Components of Participating Organizations

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Application Receipt Date(s): November 29, 2011

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) invites applications from investigators interested in participating with NICHD in an ongoing multicenter cooperative research program termed the Contraceptive Development Research Centers Program. This program is designed to expedite the development of new methods to regulate fertility. The aim of the program is to conduct a wide range of research, both basic and applied, with the ultimate goal of developing clinically useful products. Recognizing that the complexity of contraceptive development can severely limit progress achieved by individual investigators working alone, the NICHD will support up to four Centers composed of research projects and technical service core facilities that are interactively organized to conduct research to discover and develop promising new leads for regulation of fertility. The focus of individual projects may include basic, preclinical or clinical research or a combination of these areas. The Centers will also serve as a national resource for career development of young scientists electing to pursue research in contraceptive development.

Nearly half of all pregnancies in the United States are unintended. Thus, there is a critical need for fertility regulation that fits the needs of women and men throughout their reproductive lives. The ideal contraceptive should be safe and highly effective. A variety of contraceptive methods are needed to address the needs of people with different ethnic, cultural, and religious values, those with inadequate access to services, and those with changing needs related to age.

The primary objective of the Contraceptive Development Research Centers Program described in this FOA is to identify and develop new leads for regulation of fertility. There are three phases to development of new contraceptive methods: basic discovery, proof of concept, and clinical development. New products are needed that act not only as contraceptives, but also to prevent or limit sexually transmitted diseases.

The intent of this program is to establish or maintain an organizational infrastructure that has the scientific and administrative capabilities to address the broad issue of fertility regulation. Approaches to both male and female targets are encouraged. Research on abortion will not be funded.

Research projects can be directed to male or female targets of fertility regulation. The Center must consist of three or more projects, an administrative core, and optional additional core facilities capable of interacting in a coordinated, cooperative fashion. It is expected that activities may require collaboration with other institutions or other Centers. By using an interdisciplinary approach, the Centers can conduct activities that are beyond the capabilities of individual investigators or institutions.

Examples of possible research projects or cores may include but are not limited to:

  • Clinical trials for safety and efficacy of new agents with promising contraceptive properties.

  • The pharmacology of a new contraceptive agent. Pharmacological assessment may involve animal and clinical studies.

  • Hormonal, immunologic or pharmacologic methods that control gamete production, maturation or function.

  • Translational research designed to develop a promising target and/or agent into a product suitable for testing in clinical setting.

  • Research on a particular gamete-specific target for drug discovery and development.

  • Research on specific reproductive tract/system target for drug discovery and development.

  • Medicinal chemistry component in support of drug design and synthesis.

  • Integrated computational/modeling, fragment library screening, structure biology, medicinal chemistry and biological screening infrastructures for structure based drug discovery (SBDD).

  • Small molecule lead discovery through screening targeted and natural product compound libraries.

  • Screening non-traditional sources of natural products.

  • Development of genomic or proteomic screens designed to identify and define the functional role of proteins in fertilization.

  • The characterization of a macromolecule(s) involved in fertilization, the perturbation of which with a pharmacological reagent results in reversible infertility.

  • Defining specific targets involved in control of fertility through research on the processes of gamete maturation.

  • The development of a new spermicide with dual microbicidal activity.

  • The development of a novel formulation or delivery vehicle (implant, transdermal, vaginal ring, microsphere, etc.) to deliver contraceptive drugs would be considered a separate project.

A Center application can build its research strategy primarily on one broad approach to fertility regulation within which the projects are embedded, or a Center application could be structured with research representing different approaches to fertility regulation. Alternatively, an application can encompass an integrated multidisciplinary Center for target discovery and drug discovery and development in the regulation of fertility. Further, it is understood that the ultimate goal of Center's programs is to discover, develop and obtain approval of new products to regulate fertility. Therefore, the proposed projects should be components within the roadmap of discovery through approval of a drug product. The overall Center plan should stress internal priorities and collaboration and be focused on opportunities for progress and ultimately the drug product. The Center should encourage career development for new investigators in contraceptive research.

The minimal requirements for a Center as described in this FOA are as follows:

  • Competent and experienced PD/PI to oversee cooperation within the Center and to coordinate career development opportunities within the Center;

  • Competent and experienced investigators to direct individual research projects or core facilities associated with the proposed Center;

  • Availability of the technical resources and facilities for the conduct of the proposed projects, including appropriate animal facilities;

  • Research environment conducive for the development of new investigators in contraceptive research;

  • Willingness to engage in a coordinated cooperative research program involving two or more Centers with multiple interacting research projects and, if required, service cores;

  • Substantive evidence of departmental and institutional support for and commitment to the proposed Center.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving Institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Subcontracts from domestic entities to foreign sites are permitted for subprojects and cores. https://nihguide.nih.gov/Documents/Forms/AllItems.aspx

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-12-185.html.

MECHANISTIC STUDIES OF HIV-EXPOSED SERONEGATIVE INDIVIDUALS (HESN) (R21): PA-11-217

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases

National Institute on Drug Abuse

Application Receipt/Submission Date(s): Multiple dates, see announcement

The purpose of this initiative is to support mechanistic studies of individuals who are repeatedly exposed to HIV but remain seronegative (HESN), or demonstrate resistance to infection. Projects supported under this FOA could involve cellular, structural and systems biology; host and viral genetics; immunology, or virology. All projects focusing on the phenomenon of HESNs are encouraged, including those involving mechanisms responsible for establishing and maintaining seronegativity or resistance to infection, new assay development, mathematical, cell, and animal model development, and development of new technologies needed for expansion of our understanding of HESNs. Applicants are encouraged to show how proposed studies will explore the mechanisms underlying HIV seronegativity or resistance.

Over the last decade HIV infection has become a manageable and chronic disease due to highly effective antiviral treatment. Fully effective prevention strategies have been a more elusive goal. Understanding the earliest events during HIV transmission is critical to the design of an effective HIV vaccine and for improving promising microbicide strategies. Through cohort studies individuals have been identified who appear resistant to infection, or who remain seronegative after repeated HIV exposure, but few studies have tackled the difficult problem of identifying host or viral factors that account for the failure of a host to become infected despite repeated or prolonged HIV exposure. Thought-provoking observations have shown correlations of seronegativity or resistance, with: IgA qualitative and quantitative variation, serpin-protein family over expression at the genital mucosa, allo-immunity, HLA alleles, etc. With the exception of the delta 32 homozygous mutations in the CCR5 gene, the HESN studies have been associative without mechanistic data that might predict prevention strategies applicable to larger at-risk populations.

A July 2010 "Workshop on HIV "Exposed and Resistant" sponsored by the Office of AIDS Research (OAR), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute on Drug Abuse (NIDA) at the NIH, highlighted the gaps, challenges, and potential benefits of these studies (http://www.liebertonline.com/doi/abs/10.1089/AID.2010.0313). It is expected that research supported by this FOA will determine if there are mechanisms responsible for the HESN phenotype that could inform new approaches to prevention strategy challenges.

Applicants should propose hypothesis-driven specific aims that directly address one or more of the objectives below. The range of research plans may be broad; however, each application must clearly describe how the proposed study would lead to a new approach, or improve existing concepts that could lead to the design of an effective prevention strategy to reduce or eliminate HIV acquisition or infection.

Research projects and studies should address one or more of the following questions and/or topics and be directed toward identifying mechanisms rather than associations:

  • What mucosal parameters are distinctly different in the resistant population compared with those exposed in sero-converted populations?

  • What is the nature of the HESN immune response on exposure to HIV?

  • Are there host features (proteins/expression, patterns/genes) or viral features that are responsible for resistance? Studies on association of new genes, host factors, and gene expression patterns with the HESN phenotype must propose to also identify mechanism(s) involved in protection and/or defense from HIV. The ultimate goal is to identify a defensive factor that could be converted into an HIV prevention product.

  • Development of new assays and animal models to accelerate mechanistic studies, including humanized mice and non-human primates.

  • Development of new mathematical/epidemiological models to measure HIV exposure risk in men who have sex with men (MSMs), discordant couples, and female and male sex workers.

  • Exploration of the potential relationship between drug use and HESNs

Note: The areas below are NOT areas AI is seeking through this FOA. If an applicant has scientific topics in the following areas please apply thru the parent FOA: http://grants.nih.gov/grants/guide/pa-files/PA-10-067.html:

  • Clinical trials

  • Drug Development

  • Cohort development; however, recruitment of study subjects from existing cohorts is encouraged (please discuss with program)

  • Associative studies that propose solely to identify new genes but do not propose how the mechanism of protection and/or resistance will be investigated

  • Acute infection studies

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving Institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-217.html.

MECHANISTIC STUDIES OF HIV-EXPOSED SERONEGATIVE INDIVIDUALS (HESN) (R01): PA-11-218

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases

National Institute on Drug Abuse

Application Receipt/Submission Date(s): Multiple dates, see announcement

The purpose of this initiative is to support mechanistic studies of individuals who are repeatedly exposed to HIV but remain seronegative (HESN), or demonstrate resistance to infection. Projects supported under this FOA could involve cellular, structural and systems biology; host and viral genetics; immunology, or virology. All projects focusing on the phenomenon of HESNs are encouraged, including those involving mechanisms responsible for establishing and maintaining seronegativity or resistance to infection, new assay development, mathematical, cell, and animal model development, and development of new technologies needed for expansion of our understanding of HESNs. Applicants are encouraged to show how proposed studies will explore the mechanisms underlying HIV seronegativity or resistance.

Over the last decade HIV infection has become a manageable and chronic disease due to highly effective antiviral treatment. Fully effective prevention strategies have been a more elusive goal. Understanding the earliest events during HIV transmission is critical to the design of an effective HIV vaccine and for improving promising microbicide strategies. Through cohort studies individuals have been identified who appear resistant to infection, or who remain seronegative after repeated HIV exposure, but few studies have tackled the difficult problem of identifying host or viral factors that account for the failure of a host to become infected despite repeated or prolonged HIV exposure. Thought-provoking observations have shown correlations of seronegativity or resistance, with: IgA qualitative and quantitative variation, serpin-protein family over expression at the genital mucosa, allo-immunity, HLA alleles, etc. With the exception of the delta 32 homozygous mutations in the CCR5 gene, the HESN studies have been associative without mechanistic data that might predict prevention strategies applicable to larger at-risk populations.

A July 2010 "Workshop on HIV - Exposed and Resistant" sponsored by the Office of AIDS Research (OAR), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute on Drug Abuse (NIDA) at the NIH, highlighted the gaps, challenges, and potential benefits of these studies (http://www.liebertonline.com/doi/abs/10.1089/AID.2010.0313). It is expected that research supported by this FOA will determine if there are mechanisms responsible for the HESN phenotype that could inform new approaches to prevention strategy challenges.

Applicants should propose hypothesis-driven specific aims that directly address one or more of the objectives below. The range of research plans may be broad; however, each application must clearly describe how the proposed study would lead to a new approach, or improve existing concepts that could lead to the design of an effective prevention strategy to reduce or eliminate HIV acquisition or infection.

Research projects and studies should address one or more of the following questions and/or topics and be directed toward identifying mechanisms rather than associations:

  • What mucosal parameters are distinctly different in the resistant population compared with those exposed in sero-converted populations?

  • What is the nature of the HESN immune response on exposure to HIV?

  • Are there host features (proteins/expression, patterns/genes) or viral features that are responsible for resistance? Studies on association of new genes, host factors, and gene expression patterns with the HESN phenotype must propose to also identify mechanism(s) involved in protection and/or defense from HIV. The ultimate goal is to identify a defensive factor that could be converted into an HIV prevention product.

  • Development of new assays and animal models to accelerate mechanistic studies, including humanized mice and non-human primates.

  • Development of new mathematical/epidemiological models to measure HIV exposure risk in men who have sex with men (MSMs), discordant couples, and female and male sex workers.

  • Exploration of the potential relationship between drug use and HESNs

Note: The areas below are NOT areas AI is seeking through this FOA. If an applicant has scientific topics in the following areas please apply thru the parent FOA: http://grants.nih.gov/grants/guide/pa-files/PA-10-067.html:

  • Clinical trials

  • Drug Development

  • Cohort development; however, recruitment of study subjects from existing cohorts is encouraged (please discuss with program)

  • Associative studies that propose solely to identify new genes but do not propose how the mechanism of protection and/or resistance will be investigated

  • Acute infection studies

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving Institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-218.html.

EARLY PHASE CLINICAL TRIALS IN IMAGING AND IMAGE-GUIDED INTERVENTIONS (R21): PAR-11-216

Components of Participating Organizations

National Cancer Institute

Application Receipt/Submission Date(s): July 27, 2011; November 10, 2011; March 13, 2012; July 11, 2012; November 13, 2012; March 13, 2013; July 11, 2013; November 13, 2013; March 13, 2014

Imaging is a vital tool in all aspects of the clinical management of cancer including screening, diagnosis, interventions, and monitoring of responses to therapy and surveillance. Great strides have been made in the understanding of the biology and pathophysiology of cancer due to the advent of sophisticated imaging techniques.

There has been a significant investment of resources by the NCI in imaging, for both the understanding of cancer biology and the improvement of the clinical management of cancer patients. This investment has stimulated considerable additional research activity in the fields of new imaging devices, imaging agent development, and image-guided intervention (IGI), systems, methodologies, and therapies. Consequently, there are now many new approaches in cancer imaging and IGI at the preclinical stage of development. As agents, modalities and methodologies go through preclinical evaluations with promising results, they need to be further developed, utilized, and subsequently validated in clinical settings to allow for better tumor diagnosis, staging, intervention, and monitoring of response to therapy in both the general population and underserved populations. For instance, functional imaging methods that would provide clinicians with a better understanding of the effects of a given treatment, at time-points early enough to impact treatment selection and overall management, will allow treatments to be tailored to the individual patient. Early understanding of the effects of a given therapy or intervention could potentially allow clinicians to switch to more effective treatments saving patients from untoward side effects or death, saving both lives and resources. Early clinical trials of novel imaging agents and methodologies are needed to establish their safety and efficacy, as well as to advance scientific understanding of their clinical potentials. In addition, in many cases incorporation of advanced imaging and IGI techniques into clinical trials remains difficult, not in-pace with clinical need, and under supported. Hence, there is a critical need for a funding initiative for early phase trials which helps accelerate the assessment of imaging modalities, methodologies, and agents as well as IGI methods through the early stages of clinical evaluation in both the general and underserved populations.

This FOA will provide a mechanism by which to accelerate the development of these modalities, methodologies, and agents through the early stages of clinical development. This FOA will provide investigators with support for pilot (Phase I and II) cancer clinical trials, inclusive of patient monitoring and relevant laboratory studies. The imaging and Image-guided Intervention (IGI) investigations, if proven successful in these early clinical trials, can then be validated in larger studies through competitive R01 mechanisms, or through clinical trials in the Specialized Programs of Research Excellence (SPOREs), Cancer Centers, and/or Cooperative Groups.

Functional imaging and image-guided interventions that will help address health issues and disparities in underserved populations will also be considered for this FOA. Examples of issues that can be examined include, but are not limited to, novel imaging or image-guided approaches to evaluate differences in safety and efficacy of imaging agents and monitoring of differences in response to therapy among different racial and ethnic populations.

Features of this program include a modular budget and inclusion of the clinical protocol within the grant application. Inclusion of the complete clinical protocol within the human subjects section of the application is important and will ensure proper peer review of the application. Though not required, a copy of the corresponding Institutional Review Board (IRB) application can be submitted with this application to facilitate completion of the proposed research in the 2-year timeframe. Other key features include no requirement for extensive preliminary data in the application (although applicants must demonstrate that the proposed imaging or IGI solutions are ready for use in human subjects, prior to award), support for exploratory translational research studies, and rapid development and application of novel clinical imaging and IGI in cancer-related applications.

Applications that exclusively address phantom and pre-clinical studies will not be considered appropriate for this FOA.

Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving Institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than Federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

  • Central Contractor Registration (CCR) - must maintain an active registration, to be renewed at least annually

  • Grants.gov

  • eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide. Applicants may submit a resubmission, but such applications must include an Introduction addressing issues raised in the previous critique (Summary Statement).

Exploratory/developmental grant support is for new projects only; Renewal applications will not be accepted. Applicants may submit more than one application, provided each application is scientifically distinct.

Complete details at http://grants.nih.gov/grants/guide/pa-files/PAR-11-216.html.

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